Rapidly Growing Mycobacterium tuberculosis in the Form of Empyema Necessitans: A Case Report.

We present a case of rapidly growing disseminated Mycobacterium tuberculosis (MTB) that presented as an empyema necessitans (EN) in a 65-year-old woman with a single right lung transplant admitted for progressive dyspnea. While hospitalized, she had daily fevers and was found to have a right-sided chest wall abscess and pleural effusion. Acid-fast bacilli cultures from the abscess and pleural fluid grew MTB within 4 and 6 days, respectively. Blood cultures later grew MTB as well. Upon initiation of rifampin, isoniazid, pyrazinamide, and ethambutol, she developed hemorrhagic pancreatitis and distributive shock secondary to antituberculosis medications and disseminated MTB. Noteworthy features of this case include the rapid rate of MTB culture growth in less than a week, the development of a likely donor-derived MTB EN, and the clinical challenges of MTB screening and MTB infection management in a solid organ transplant recipient.

Pembrolizumab-Induced Diabetic Ketoacidosis: A Review of Critical Care Case.

Diabetic ketoacidosis (DKA) is a commonly encountered diagnosis in the general inpatient and intensive care unit settings. We report a rare case of pembrolizumab-induced DKA in a patient with bladder carcinoma in situ with no prior diagnosis of diabetes. Our case highlights the importance of understanding immune-related adverse events (IRAEs) as immunotherapy is becoming a mainstay of treatment for a variety of diagnoses. The rare side effect of DKA presented in this case is compared to the classical presentation of DKA secondary to type 1 diabetes mellitus (T1DM). We found that pembrolizumab-induced DKA presented with fewer symptoms than T1DM-induced DKA and did not present with serum antibodies that are typically present in T1DM. While management of DKA in the acute setting is unchanged regardless of the precipitating factor, this case demonstrates the importance of identifying the precipitant in order to pursue the appropriate diagnostic workup and long-term management.

Allogeneic cardiosphere-derived cells (CAP-1002) in critically ill COVID-19 patients: compassionate-use case series.

There are no definitive therapies for patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Therefore, new therapeutic strategies are needed to improve clinical outcomes, particularly in patients with severe disease. This case series explores the safety and effectiveness of intravenous allogeneic cardiosphere-derived cells (CDCs), formulated as CAP-1002, in critically ill patients with confirmed coronavirus disease 2019 (COVID-19). Adverse reactions to CAP-1002, clinical status on the World Health Organization (WHO) ordinal scale, and changes in pro-inflammatory biomarkers and leukocyte counts were analyzed. All patients (n = 6; age range 19-75 years, 1 female) required ventilatory support (invasive mechanical ventilation, n = 5) with PaO2/FiO2 ranging from 69 to 198. No adverse events related to CAP-1002 administration were observed. Four patients (67%) were weaned from respiratory support and discharged from the hospital. One patient remains mechanically ventilated as of April 28th, 2020; all survive. A contemporaneous control group of critically ill COVID-19 patients (n = 34) at our institution showed 18% overall mortality at a similar stage of hospitalization. Ferritin was elevated in all patients at baseline (range of all patients 605.43-2991.52 ng/ml) and decreased in 5/6 patients (range of all patients 252.89-1029.90 ng/ml). Absolute lymphocyte counts were low in 5/6 patients at baseline (range 0.26-0.82 × 103/µl) but had increased in three of these five patients at last follow-up (range 0.23-1.02 × 103/µl). In this series of six critically ill COVID-19 patients, intravenous infusion of CAP-1002 was well tolerated and associated with resolution of critical illness in 4 patients. This series demonstrates the apparent safety of CAP-1002 in COVID-19. While this initial experience is promising, efficacy will need to be further assessed in a randomized controlled trial.

A Case Series of Vaping-Associated Lung Injury Requiring Mechanical Ventilation.

OBJECTIVES: Vaping-associated lung injury has rapidly become a nationwide epidemic and a threat to public health. In this case series, we describe unique clinical features of severe vaping-associated lung injury, defined as respiratory failure due to vaping that requires mechanical ventilation. DATA SOURCES: Clinical observation of four patients. STUDY SELECTION: Case series. DATA EXTRACTION: Data and images were extract from medical records after approval was obtained from the institutional review board. DATA SYNTHESIS: Four patients were admitted to the ICU with severe manifestation of vaping-associated lung injury. Although every case required mechanical ventilatory support (venovenous extracorporeal membrane oxygenation in one patient), all patients survived and were discharged without supplemental oxygen. Systemic corticosteroids were administered in three patients and N-acetyl cysteine in one. A postdischarge pulmonary function test in one patient was normal except for mildly decreased diffusing capacity. CONCLUSIONS: Based on our experience, prognosis of severe vaping-associated lung injury appears favorable with aggressive supportive care, although there is evidence from existing literature that mortality rate might rise with increasing disease severity. Underlying mechanism of lung injury might be similar between vaping-associated lung injury and amiodarone pneumonitis. Foamy or lipid-laden macrophages, seen in both conditions, might be a marker of cytotoxicity from substances contained in e-cigarettes, such as vitamin E acetate. Systemic corticosteroids, and possibly N-acetyl cysteine, could be considered as therapeutic adjuncts in vaping-associated lung injury. Serial pulmonary function tests should be obtained in these patients to monitor for potential long-term complications. The primary limitations of this case series are its small sample and lack of longitudinal follow-up data.

Pharmacological management of progressive-fibrosing interstitial lung diseases: a review of the current evidence.

A proportion of patients with interstitial lung diseases (ILDs) are at risk of developing a progressive-fibrosing phenotype, which is associated with a deterioration in lung function and early mortality. In addition to idiopathic pulmonary fibrosis (IPF), fibrosing ILDs that may present a progressive phenotype include idiopathic nonspecific interstitial pneumonia, connective tissue disease-associated ILDs, hypersensitivity pneumonitis, unclassifiable idiopathic interstitial pneumonia, ILDs related to other occupational exposures and sarcoidosis. Corticosteroids and/or immunosuppressive therapies are sometimes prescribed to patients with these diseases. However, this treatment regimen may not be effective, adequate on its own or well tolerated, suggesting that there is a pressing need for efficacious and better tolerated therapies. Currently, the only approved treatments to slow disease progression in patients with IPF are nintedanib and pirfenidone. Similarities in pathobiological mechanisms leading to fibrosis between IPF and other ILDs that may present a progressive-fibrosing phenotype provide a rationale to suggest that nintedanib and pirfenidone may be therapeutic options for patients with the latter diseases.This review provides an overview of the therapeutic options currently available for patients with fibrosing ILDs, including fibrosing ILDs that may present a progressive phenotype, and explores the status of the randomised controlled trials that are underway to determine the efficacy and safety of nintedanib and pirfenidone.

The inspiratory capacity/total lung capacity ratio as a predictor of survival in an emphysematous phenotype of chronic obstructive pulmonary disease.

BACKGROUND: Forced expiratory volume in 1 second (FEV1) grades severity of COPD and predicts survival. We hypothesize that the inspiratory capacity/total lung capacity (IC/TLC) ratio, a sensitive measure of static lung hyperinflation, may have a significant association with survival in an emphysematous phenotype of COPD. OBJECTIVES: To access the association between IC/TLC and survival in an emphysematous phenotype of COPD. METHODS: We performed a retrospective analysis of a large pulmonary function (PF) database with 39,050 entries, from April 1978 to October 2009. Emphysematous COPD was defined as reduced FEV1/forced vital capacity (FVC), increased TLC, and reduced diffusing capacity of the lungs for carbon monoxide (DLCO; beyond 95% confidence intervals [CIs]). We evaluated the association between survival in emphysematous COPD patients and the IC/TLC ratio evaluated both as dichotomous (≤25% vs >25%) and continuous predictors. Five hundred and ninety-six patients had reported death dates. RESULTS: Univariate analysis revealed that IC/TLC ≤25% was a significant predictor of death (hazard ratio [HR]: 2.39, P<0.0001). Median survivals were respectively 4.3 (95% CI: 3.8-4.9) and 11.9 years (95% CI: 10.3-13.2). Multivariable analysis revealed age (HR: 1.19, 95% CI: 1.14-1.24), female sex (HR: 0.69, 95% CI: 0.60-0.83), and IC/TLC ≤25% (HR: 1.69, 95% CI: 1.34-2.13) were related to the risk of death. Univariate analysis showed that continuous IC/TLC was associated with death, with an HR of 1.66 (95% CI: 1.52-1.81) for a 10% decrease in IC/TLC. CONCLUSION: Adjusting for age and sex, IC/TLC ≤25% is related to increased risk of death, and IC/TLC as a continuum, is a significant predictor of mortality in emphysematous COPD patients.

Esophageal motor dysfunction and gastroesophageal reflux are prevalent in lung transplant candidates.

BACKGROUND: Gastroesophageal reflux and aspiration contribute to the development of bronchiolitis obliterans and accelerate graft deterioration after lung transplantation (LTx). We evaluated LTx candidates for esophageal motor abnormalities and gastroesophageal reflux. METHODS: Consecutive patients evaluated for LTx underwent 24-hour pH monitoring using a dual-channel pH probe and high-resolution esophageal manometry. High-resolution manometry was also performed in healthy control subjects. The prevalence of abnormal acid exposure was noted in the LTx candidates. RESULTS: Thirty LTx candidates and 10 control subjects were evaluated. Lung transplantation candidates had higher residual upper and lower esophageal sphincter pressures. The mean proportion of peristaltic swallows was 21% lower in LTx candidates. Both hypotensive and aperistaltic swallows were sixfold more prevalent in LTx candidates than in control subjects. All control subjects had normal high-resolution manometry whereas 23 LTx candidates (76.7%) had esophageal peristaltic dysfunction. Abnormal acid exposure time was seen in the proximal and distal esophagus in 25% and 36% of LTx candidates, respectively. Lung transplantation candidates with idiopathic pulmonary fibrosis had more aperistaltic contractions, more negative minimum intrathoracic pressure, and a higher frequency of abnormal distal esophagus acid exposure. The majority of patients with complications after LTx demonstrated motor, anatomic, or pH abnormalities. CONCLUSIONS: Disordered esophageal motor function and gastroesophageal reflux are common in LTx candidates. We believe high-resolution esophageal manometry is a valid tool to use and the abnormalities we identified may be representative of this unique patient population. The role of this study in predicting a worse outcome should be further studied in patients after LTx.

The emergence of oral tadalafil as a once-daily treatment for pulmonary arterial hypertension.

Pulmonary hypertension (PH) is found in a vast array of diseases, with a minority representing pulmonary arterial hypertension (PAH). Idiopathic PAH or PAH in association with other disorders has been associated with poor survival, poor exercise tolerance, progressive symptoms of dyspnea, and decreased quality of life. Left untreated, patients with PAH typically have a progressive decline in function with high morbidity ultimately leading to death. Advances in medical therapy for PAH over the past decade have made significant inroads into improved function, quality of life, and even survival in this patient population. Three classes of pulmonary artery-specific vasodilators are currently available in the United States. They include prostanoids, endothelin receptor antagonists, and phosphodiesterase type 5 (PDE5) inhibitors. In May 2009, the FDA approved tadalafil, the first once-daily PDE5 inhibitor for PAH. This review will outline the currently available data on tadalafil and its effects in patients with PAH.

Overview of the perioperative management of lung volume reduction surgery patients.

This article reviews management strategies that may improve the outcome of thoracic surgery and particularly lung volume reduction surgery (LVRS) in patients with severe emphysema. Maximal preoperative pharmacologic therapy includes bronchodilators and inhaled corticosteroids to attain peak lung function at the time of surgery. Nonpharmacologic measures include smoking cessation and pulmonary rehabilitation. Mechanical ventilation during the perioperative period should ensure adequate oxygenation, while avoiding dynamic hyperinflation. Keys to successful postoperative care include close monitoring while in the intensive care unit, early extubation, adequate pain control, chest physiotherapy and appropriate chest tube management. Aggressive management of early postoperative complications, including air leaks, respiratory failure, arrhythmias, and hemorrhage, can also be expected to improve outcomes.

Inhaled and systemic corticosteroids in chronic obstructive pulmonary disease.

Systemic and local inflammation is central to the pathophysiology of chronic obstructive pulmonary disease (COPD). Increased levels of inflammation have been linked to a more progressive course in COPD and have been shown to be present during an exacerbation. Decreases in inflammatory cytokines, C-reactive protein, and inflammatory cells have been observed with corticosteroid use, suggesting a possible mechanism for a therapeutic benefit of steroids. No available data support the routine use of systemic corticosteroids in stable COPD; however, short courses during exacerbations are likely to improve length of hospitalization, lung function, and relapse rate. Inhaled corticosteroids (ICS) decrease the rate of exacerbation and may improve the response to bronchodilators and decrease dyspnea in stable COPD. No study shows that ICS reduce the loss of lung function; however, recent data suggest a possible survival benefit when combined with long-acting beta agonists. There are limited data on the use of ICS in the treatment of acute exacerbations of COPD, and its role in this setting must be more clearly defined. The empiric use of systemic corticosteroids perioperatively represents another area of uncertainty. The role of pharmacogenetics in the metabolism of corticosteroids in COPD is evolving but may be partially responsible for the observed variability in patient responsiveness. The potential benefits of systemic or inhaled corticosteroid use must be weighed against the risk of known toxicities.

Cardiac disease in chronic obstructive pulmonary disease.

The cardiac manifestations of chronic obstructive pulmonary disease (COPD) are numerous. Impairments of right ventricular dysfunction and pulmonary vascular disease are well known to complicate the clinical course of COPD and correlate inversely with survival. The pathogenesis of pulmonary vascular disease in COPD is likely multifactorial and related to alterations in gas exchange and vascular biology, as well as structural changes of the pulmonary vasculature and mechanical factors. Several modalities currently exist for the assessment of pulmonary vascular disease in COPD, but right heart catheterization remains the gold standard. Although no specific therapy other than oxygen has been generally accepted for the treatment of pulmonary hypertension in this population, there has been renewed interest in specific pulmonary vasodilators. The coexistence of COPD and coronary artery disease occurs frequently. This association is likely related to shared risk factors as well as similar pathogenic mechanisms, such as systemic inflammation. Management strategies for the care of patients with COPD and coronary artery disease are similar to those without COPD, but care must be given to address their respiratory limitations. Arrhythmias occur frequently in patients with COPD, but are rarely fatal and can generally be treated medically. Use of beta-blockers in the management of cardiac disease, while a theoretical concern in patients with increased airway resistance, is generally safe with the use of cardioselective agents.

Lung elastic recoil does not correlate with pulmonary hemodynamics in severe emphysema.

BACKGROUND: It has been postulated that right ventricular (RV) function may improve after lung volume reduction surgery (LVRS) for severe emphysema due to improvement in lung elastic recoil. Improved lung elastic recoil after LVRS is hypothesized to "tether" open extraalveolar vessels, thereby leading to a decrease in pulmonary vascular resistance (PVR) and improved RV function. Whether a relationship exists between static elastic lung recoil and pulmonary hemodynamics in severe emphysema, however, is unknown. METHODS: We prospectively studied 67 patients with severe emphysema (32 women; mean age, 65.3+/-6.6 years [SD]; mean FEV1, 0.79+/-0.25 L) who had hyperinflation (total lung capacity [TLC], 122.5+/-12.3% of predicted) and gas trapping (residual volume, 209.1+/-41.1% of predicted), and were referred to the National Emphysema Treatment Trial. Lung elastic recoil was measured both at TLC (coefficient of retraction [CR]) and at functional reserve capacity (CR at functional residual capacity [CRfrc]) in each patient. RESULTS: CR and CRfrc values were 1.3+/-0.6 cm H2O/L and 0.61+/-0.5 cm H2O/L, respectively. Hemodynamic measurements revealed a pulmonary artery (PA) systolic pressure of 35.9+/-8.9 mm Hg, mean PA pressure of 24.8+/-5.6 mm Hg, and PVR of 174+/-102 dyne*s*cm(-5). No significant correlations were found between CR and PVR (R=-0.046, p=0.71), PA systolic pressure (R=0.005, p=0.97), or mean PA pressure (R=-0.028, p=0.82). Additionally, no significant correlations were found between CRfrc and PVR (R=-0.002, p=0.99), PA systolic pressure (R=-0.062, p=0.62), or mean PA pressure (R=-0.041, p=0.74). CONCLUSIONS: We conclude there is no correlation between lung elastic recoil and pulmonary hemodynamics in severe emphysema, suggesting that elastic lung recoil is not an important determinant of secondary pulmonary hypertension in this group. Registered with www. clinicaltrials.gov, #NCT00000606.

Effect of lung volume reduction surgery on resting pulmonary hemodynamics in severe emphysema.

RATIONALE: To determine the effect of medical treatment versus lung volume reduction surgery (LVRS) on pulmonary hemodynamics. METHODS: Three clinical centers of the National Emphysema Treatment Trial (NETT) screened patients for additional inclusion into a cardiovascular (CV) substudy. Demographics were determined, and lung function testing, six-minute-walk distance, and maximum cardiopulmonary exercise testing were done at baseline and 6 months after medical therapy or LVRS. CV substudy patients underwent right heart catheterization at rest prerandomization (baseline) and 6 months after treatment. MEASUREMENTS AND MAIN RESULTS: A total of 110 of the 163 patients evaluated for the CV substudy were randomized in NETT (53 were ineligible), 54 to medical treatment and 56 to LVRS. Fifty-five of these patients had both baseline and repeat right heart catheterization 6 months postrandomization. Baseline demographics and lung function data revealed CV substudy patients to be similar to the remaining 1,163 randomized NETT patients in terms of age, sex, FEV(1), residual volume, diffusion capacity of carbon monoxide, Pa(O(2)), Pa(CO(2)), and six-minute-walk distance. CV substudy patients had moderate pulmonary hypertension at rest (Ppa, 24.8 +/- 4.9 mm Hg); baseline hemodynamic measurements were similar across groups. Changes from baseline pressures to 6 months post-treatment were similar across treatment groups, except for a smaller change in pulmonary capillary wedge pressure at end-expiration post-LVRS compared with medical treatment (-1.8 vs. 3.5 mm Hg, p = 0.04). CONCLUSIONS: In comparison to medical therapy, LVRS was not associated with an increase in pulmonary artery pressures.

Treatment of Guillain-Barré syndrome induced by cyclosporine in a lung transplant patient.

We report the case of a 58-year-old man with severe chronic obstructive pulmonary disease who developed acute quadriparesis during the post-operative period following bilateral lung transplantation after receiving cyclosporine for immunosuppression. Electromyography with nerve conduction study and cerebrospinal fluid analysis supported a diagnosis of Guillain-Barré Syndrome, which improved upon the discontinuation of cyclosporine, replacement with tacrolimus, and initiation of plasmapheresis. We propose the discontinuation of cyclosporine and initiation of plasmapheresis as a treatment for cyclosporine-associated Guillain-Barré syndrome.