Systemic lupus-induced diffuse alveolar hemorrhage treated with extracorporeal membrane oxygenation: a case report and review of the literature.

OBJECTIVES: We report the case of a 28-year-old patient with systemic lupus erythematosus (SLE) with rapid onset of dyspnea and hemoptysis found to have diffuse alveolar hemorrhage (DAH) with refractory hypoxemia successfully treated with venovenous extracorporeal membrane oxygenation (ECMO). The discussion includes clinical presentation, diagnosis, management, outcome, and a review of the available adult literature on the use of ECMO in patients with DAH. DESIGN: Case report. SETTING: Froedtert Hospital and the Medical College of Wisconsin. DATA SOURCES: Data were collected from the patient's electronic medical record and the hospital radiology database. CONCLUSIONS: Diffuse alveolar hemorrhage secondary to SLE is quite rare. The adult literature on the utilization of ECMO for DAH is limited mostly to antineutrophil cytoplasmic antibody (ANCA)-associated alveolar hemorrhage and a few reports of nonvasculitis DAH. Bleeding has been a contraindication to ECMO due to the need for systemic anticoagulation. Our case, along with a review of the literature, indicates that ECMO with anticoagulation can be safely utilized in patients with DAH. To our knowledge, this is the first reported adult case of DAH due to SLE successfully treated with ECMO.

Daptomycin-induced acute eosinophilic pneumonia.

INTRODUCTION: Daptomycin is a cyclic lipopeptide antibiotic with activity against gram-positive organisms. With increasing use, acute eosinophilic pneumonia is a rare, but potentially fatal adverse drug reaction that requires prompt recognition. The authors present a definite case of daptomycin-induced acute eosinophilic pneumonia. CASE SUMMARY: A 61-year-old woman with poorly controlled type 2 diabetes who presented with bilateral foot pain was found to have bilateral calcaneal osteomyelitis. She was started on an antibiotic regimen that included daptomycin. Within 1 week, she developed fever, a dry cough, and shortness of breath and was treated for hospital-acquired pneumonia (HAP). Daptomycin was discontinued. Upon completion of therapy for HAP, the patient was subsequently restarted on daptomycin for continued therapy of bilateral calcaneal osteomyelitis. Within 48 hours of restarting daptomycin, the patient developed hypoxemic respiratory failure, bilateral pulmonary infiltrates, and peripheral eosinophilia. Bronchoscopic lavage revealed 30% eosinophils. Daptomycin-induced acute eosinophilic pneumonia was diagnosed. Daptomycin was discontinued, and the patient had complete resolution of symptoms, peripheral eosinophilia, and radiographic findings. DISCUSSION: Daptomycin initially was approved for skin and soft tissue infections, but its utility has expanded to bacteremia and endocarditis. Daptomycin-induced acute eosinophilic pneumonia is rare. A recent Federal Drug Administration review identified a total of 58 cases of daptomycin-induced acute eosinophilic pneumonia. Of these, 38 were possible, 13 were probable, and 7 were definite. We believe this is the 8th definite case of daptomycin-induced acute eosinophilic pneumonia to be reported in the literature.

Optimizing Respiratory Therapy Resources by De-Implementing Low-Value Care.

BACKGROUND: Our institution was experiencing a respiratory therapy staffing crisis during the COVID-19 pandemic, in part due to excessive workload. We identified an opportunity to reduce burden by limiting use of 3% hypertonic saline and/or N-acetylcysteine nebulizer therapies (3%HTS/NAC). METHODS: Leveraging the science of de-implementation, we established a policy empowering respiratory therapists to discontinue 3%HTS/NAC not meeting the American Association for Respiratory Care (AARC) Clinical Practice Guideline: Effectiveness of Pharmacologic Airway Clearance Therapies in Hospitalized Patients. After a 3-month period of educating physicians and advanced practice practitioners the policy went to into effect. Outcomes measured included monthly number of treatments, orders, and full-time employees associated with administering nebulized 3%HTS/NAC. RESULTS: Post policy activation, the monthly mean 3%HTS/NAC treatments were significantly reduced to 547.5 ± 284.3 from 3,565.2 ± 596.4 (P < .001) as were the associated monthly mean of full-time employees, 0.8 ± 0.41 from 5.1 ± 0.86 (P < .001). The monthly mean 3%HTS/NAC orders also fell to 93.8 ± 31.5 from 370.0 ± 46.9 (P < .001). Monthly mean non-3%HTS/NAC treatments remained stable; post policy was 3,089.4 ± 611.4 and baseline 3,279.6 ± 695.0 (P = 1.0). CONCLUSIONS: Implementing a policy that empowers respiratory therapists to promote adherence to AARC Clinical Guidelines reduced low-value therapies, costs, and staffing needs.

Clozapine-induced peripheral and pleural fluid eosinophilia.

OBJECTIVE: To present a case of clozapine-induced peripheral and pleural fluid eosinophilia (PFE). CASE SUMMARY: A 28-year-old man who was taking clozapine for bipolar disorder presented with a 2-week history of increasing shortness of breath. A large right-sided pleural effusion was identified, and eosinophilia was noted in peripheral and pleural fluid. An extensive workup ruled out other etiologies of PFE, and an objective causality assessment revealed that an adverse reaction to clozapine was probable. Clozapine was discontinued and the patient had complete resolution of symptoms, peripheral eosinophilia, and pleural effusion. DISCUSSION: Drug-induced pleural disease is uncommon. Nearly 30 drugs have been implicated as causation of pleural disease. Much less common is PFE, with only 8 drugs implicated since 2004. Clozapine is a second-generation antipsychotic approved for treatment of resistant schizophrenia. It is often also used to treat bipolar disorder. Common adverse effects include tachycardia, somnolence, weight gain, and sialorrhea. Uncommon adverse reactions include pancreatitis and agranulocytosis. Through 2009, 11 cases of clozapine-induced pleural effusion, with and without polyserositis, have been reported; however, pleural fluid studies to demonstrate eosinophilia have not been done. CONCLUSIONS: To our knowledge, this is the first documented report of clozapine-induced peripheral eosinophilia and PFE. Clinicians should consider clozapine as a possible cause of these reactions.

A 28-day clinical trial of aerosolized hyaluronan in alpha-1 antiprotease deficiency COPD using desmosine as a surrogate marker for drug efficacy.

INTRODUCTION: A previous 2-week clinical trial of aerosolized hyaluronan (HA) in COPD showed a rapid reduction in lung elastic fiber breakdown, as measured by sputum levels of the unique elastin crosslinks, desmosine and isodesmosine (DID). To further assess the therapeutic efficacy of HA and the utility of DID as surrogate markers for the development of pulmonary emphysema, we have conducted a 28-day randomized, double-blind, placebo-controlled, phase 2 trial of HA involving 27 subjects with alpha-1 antiprotease deficiency COPD. METHODS: The study drug consisted of a 3 ml inhalation solution containing 0.03% HA with an average molecular weight of 150 kDa that was self-administered twice daily. DID levels were measured in urine, sputum, and plasma using tandem mass spectrometry. RESULTS: Free urine DID in the HA group showed a significant negative correlation with time between days 14 and 35 (r = -1.0, p = 0.023) and was statistically significantly decreased from baseline at day 35 (15.4 vs 14.2 ng/mg creatinine, p = 0.035). A marked decrease in sputum DID was also seen in the HA group between days 1 and 28 (0.96 vs 0.18 ng/mg protein), but the difference was not significant, possibly due to the small number of adequate specimens. Plasma DID remained unchanged following HA treatment and no significant reductions in urine, sputum, or plasma DID were seen in the placebo group. CONCLUSIONS: The results support additional clinical trials to further evaluate the therapeutic effect of HA and the use of DID as a real-time marker of drug efficacy.

Risk factors for bronchiolitis obliterans in allogeneic hematopoietic stem-cell transplantation for leukemia.

STUDY OBJECTIVES: Reported risk factors for bronchiolitis obliterans (BO) in allogeneic hematopoietic stem-cell transplant recipients come from modest-sized studies and are limited to experiences of single institutions. We sought to identify risk factors for BO using data from the International Bone Marrow Transplant Registry. METHODS: Registry data on 6,275 adult patients with leukemia who received human leukocyte antigen-identical sibling transplants from 1989 to 1997 and survived at least 100 days after transplantation were evaluated for the study. Risk factors for BO were analyzed using proportional hazards regression. RESULTS: Seventy-six patients were found to have BO, with an incidence rate of 1.7% at 2 years after transplantation. The Kaplan-Meier estimate of median time to onset of BO was 431 days. Histologic evaluation was performed in 36 patients (47%). In 28 patients (37%), diagnosis was based on pulmonary function tests, CT scans of the chest, or a combination of both. On multivariate analysis, the factors that were associated with an increased risk for BO included the following: peripheral blood-derived stem cell, a busulfan-based conditioning regimen, interval from diagnosis to transplant > or = 14 months, female donor to male recipient sex match, prior interstitial pneumonitis, and an episode of moderate-to-severe acute graft-vs-host disease (GVHD). CONCLUSION: In addition to corroborating previously reported risk factors, such as acute GVHD and a busulfan-based conditioning regimen, we found that peripheral blood stem-cell transplantation, long duration to transplant, female donor to male recipient, and a prior episode of interstitial pneumonitis are associated with an increased risk for BO.

Tracheobronchial amyloidosis managed with multimodality therapies.

Amyloidosis is a systemic disease involving abnormal extracellular deposition of amyloid and autologous fibrillar protein material in ß-pleated sheets. Accumulation of this abnormal protein leads to organ dysfunction, although respiratory tract involvement is rare. We present two cases of tracheobronchial amyloidosis successfully treated with surgery and radiation.

Restoring functional status: a long-term case report of severe lung and ventilatory muscle pump dysfunction involving recurrent bacterial pneumonias.

BACKGROUND AND PURPOSE: Prolonged mechanical ventilation contributes to immobility and deconditioning making efforts to safely discontinue ventilator support desirable. This case report documents how implementing physical therapy treatment interventions, based on the Guide to Physical Therapist Practice, can help to restore a person's functional status even after multiple years of mechanical ventilation dependency. CASE DESCRIPTION: A patient (female; aged 63 years) with severe restrictive and obstructive ventilatory impairment has survived 34 recurrent pneumonias involving 6 bacterial pathogens while being mechanically ventilated at home. A 3-year study was approved and informed consent obtained for a home exercise program of resistive extremity and inspiratory muscle training along with exercise reconditioning. Tolerable distances walked, maximal inspiratory and expiratory pressures, hours spent on versus off mechanical ventilation, activities performed within and around her home, and community excursions taken were charted. OUTCOMES: Daily time tolerated off the ventilator improved from less than one to 12 hours, distance walked in 6 minutes increased 33%, and maximal inspiratory and expiratory pressures improved 62% and 9.6% respectively. These improvements made out-of-home social excursions possible. DISCUSSION AND CONCLUSIONS: This patient's functional status improved following multiple physical therapy interventions dictated by the evaluation of initial physical therapy examination findings according to the Guide to Physical Therapist Practice. Long term mechanical ventilator dependency in the home environment did not exclude this patient from achieving clinically significant gains in functional status even when having severe restrictive and obstructive ventilator impairment.

Severe pulmonary toxicity after azathioprine/6-mercaptopurine initiation for the treatment of inflammatory bowel disease.

Azathioprine and 6-mercaptopurine (6-MP) are effective in inflammatory bowel disease (IBD). However, between 10% and 29% of patients treated with these drugs are forced to stop therapy due to side effects. Pulmonary toxicity due to azathioprine/6-MP has been reported infrequently. We describe 3 patients who developed severe, noninfectious pulmonary toxicity within 1 month after the initiation of azathioprine or 6-MP for the treatment of IBD colitis (2 Crohn's disease and 1 ulcerative colitis). All patients presented with dyspnea, cough, and fever after initiation of azathioprine/6-MP. Evaluation for infectious etiologies, including bronchoscopy (3/3 patients) and open-lung biopsy (2/3 patients) was negative. Histopathologic examination of the lung biopsies revealed bronchiolitis obliterans organizing pneumonia in one, and usual interstitial pneumonitis in another patient. Cessation of purine analog therapy resulted in clinical improvement in all 3 cases. Azathioprine/6-MP-related pulmonary toxicity is a rare but serious side effect, and it is important for clinicians to have a high index of suspicion for this adverse reaction which occurs within 1 month after initiation of treatment for IBD.

Incidence of asymptomatic pulmonary embolism in moderately to severely injured trauma patients.

BACKGROUND: Chest computed tomographic (CT) scanning is used frequently to evaluate symptomatic patients for pulmonary embolus (PE). The incidence of PE diagnosed by helical CT scanning in asymptomatic patients is unknown. METHODS: Asymptomatic trauma patients with an Injury Severity Score > or = 9 were studied with contrast-enhanced helical CT images of the chest, pelvis, and lower extremities. Clot burden was assessed using an anatomic scoring system. Patients not receiving anticoagulation were followed. RESULTS: Twenty-two of 90 patients had a PE. Four had major clot burden, including one patient with a saddle embolus. Risk factors for asymptomatic PE include age (odds ratio [OR], 1.04), head injury (OR, 6.78), chest injury (OR, 4.51), lower extremity injury (OR, 5.03), and transfusion (OR, 3.42). Thirty percent of patients receiving pharmacologic prophylaxis had a PE. CONCLUSION: Asymptomatic PE occur in 24% of moderately to severely injured patients. Age, head, chest, and lower extremity injury are associated with an increased risk. Standard thromboembolic prophylaxis is not reliably protective.