Successful Treatment of Prolonged, Severe Coronavirus Disease 2019 Lower Respiratory Tract Disease in a B cell Acute Lymphoblastic Leukemia Patient With an Extended Course of Remdesivir and Nirmatrelvir/Ritonavir.

A patient with B-cell acute lymphoblastic leukemia (ALL) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had persistent, progressive pneumonia with viremia after 5 months of infection despite monoclonal antibodies, intravenous (IV) remdesivir and prolonged oral steroids. Twenty days of nirmatrelvir/ritonavir and 10 days of IV remdesivir led to full recovery.

Death with dignity in Washington patients with amyotrophic lateral sclerosis.

OBJECTIVES: To describe the amyotrophic lateral sclerosis (ALS) patients who sought medication under the Washington State Death with Dignity (DWD) Act since its inception in 2009. METHODS: Chart review at 3 tertiary medical centers in the Seattle/Puget Sound region and comparison to publicly available data of ALS and all-cause DWD cohorts from Washington and Oregon. RESULTS: In Washington State, 39 patients with ALS requested DWD from the University of Washington, Virginia Mason, and Swedish Medical Centers beginning in 2009. The median age at death was 65 years (range 46-86). Seventy-seven percent of the patients used the prescriptions. All of the patients who used the medications passed away without complications. The major reasons for patients to request DWD as reported by participating physicians were loss of autonomy and dignity and decrease in enjoyable activities. Inadequate pain control, financial cost, and loss of bodily control were less commonly indicated. These findings were similar to those of the 92 patients who sought DWD in Oregon. In Washington and Oregon, the percentage of patients with ALS seeking DWD is higher compared to the cancer DWD cohort. Furthermore, compared to the all-cause DWD cohort, patients with ALS are more likely to be non-Hispanic white, married, educated, enrolled in hospice, and to have died at home. CONCLUSIONS: Although a small number, ALS represents the disease with the highest proportion of patients seeking to participate in DWD. Patients with ALS who choose DWD are well-educated and have access to palliative or life-prolonging care. The use of the medications appears to be able to achieve the patients' goals without complications.

An official American Thoracic Society workshop report: assessment and palliative management of dyspnea crisis.

In 2009, the American Thoracic Society (ATS) funded an assembly project, Palliative Management of Dyspnea Crisis, to focus on identification, management, and optimal resource utilization for effective palliation of acute episodes of dyspnea. We conducted a comprehensive search of the medical literature and evaluated available evidence from systematic evidence-based reviews (SEBRs) using a modified AMSTAR approach and then summarized the palliative management knowledge base for participants to use in discourse at a 2009 ATS workshop. We used an informal consensus process to develop a working definition of this novel entity and established an Ad Hoc Committee on Palliative Management of Dyspnea Crisis to further develop an official ATS document on the topic. The Ad Hoc Committee members defined dyspnea crisis as "sustained and severe resting breathing discomfort that occurs in patients with advanced, often life-limiting illness and overwhelms the patient and caregivers' ability to achieve symptom relief." Dyspnea crisis can occur suddenly and is characteristically without a reversible etiology. The workshop participants focused on dyspnea crisis management for patients in whom the goals of care are focused on palliation and for whom endotracheal intubation and mechanical ventilation are not consistent with articulated preferences. However, approaches to dyspnea crisis may also be appropriate for patients electing life-sustaining treatment. The Ad Hoc Committee developed a Workshop Report concerning assessment of dyspnea crisis; ethical and professional considerations; efficient utilization, communication, and care coordination; clinical management of dyspnea crisis; development of patient education and provider aid products; and enhancing implementation with audit and quality improvement.

What is DIPNECH?

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a rare disorder that is being diagnosed more frequently with the increasing availability of advanced imaging and more accurate histopathology. It occurs most commonly in nonsmoking, middle-aged women. High-resolution computed tomography (HRCT) findings include mosaic attenuation due to constrictive bronchiolitis and small (<5 mm) randomly distributed pulmonary nodules. It is important to recognize this condition as it is considered a precursor of peripheral carcinoid tumors. This article will present a case of this uncommon condition with review of the literature, imaging findings, and clinical presentation.

Novel uses of noninvasive ventilation.

Noninvasive ventilation (NIV) and continuous positive airway pressure (CPAP) have been used in various unusual settings to assist breathing. NIV is now frequently used to treat exacerbations of chronic obstructive pulmonary disease and chronic respiratory failure in neuromuscular disease. This paper discusses CPAP and NIV for postoperative hypoxemia, preventing intubation in high-risk bronchoscopy, respiratory failure in pandemics, obesity hypoventilation syndrome, and respiratory support during percutaneous endoscopic gastrostomy tube placement.

Pulmonary function in the morbidly obese.

BACKGROUND: Only limited data exist on the relationship of lung function to patients with extreme obesity. To assess the relationship between lung function tests and clinical characteristics in a cohort of morbidly obese patients undergoing evaluation for bariatric procedures in a university hospital in the United States. METHODS: Consecutive patients undergoing clinical evaluation were reviewed. The variables included demographic, anthropometric, clinical, and pulmonary function data. RESULTS: A total of 229 patients underwent a standardized preoperative evaluation. Of these 229 patients, 136 (59%) had evaluable data and 102 (75%) were women. The mean +/- standard deviation age was 45 +/- 10 years, the mean weight was 164 +/- 42 kg, and the mean body mass index was 57 +/- 13 kg/m2. Smoking or asthma was reported in 38% and 24% of patients, respectively. The mean forced vital capacity and forced expiratory volume in 1 s was 80% +/- 17% of predicted and 76% +/- 19% of predicted, respectively. Of the 136 patients, 29% had a measured forced expiratory volume in 1 s/forced vital capacity of >or=.08 below the predicted ratio. The mean total lung capacity was 86% +/- 14% of predicted; 26% of subjects had a total lung capacity <80% of predicted. Multivariate logistic regression analysis demonstrated an association of obstructive ventilatory defects with male gender (odds ratio [OR] 2.35, 95% confidence interval [CI] 1.00-5.50) and current or previous smoking (OR 2.41, 95% CI 1.10-5.30), but not body mass index. Restrictive defects were associated with body mass index (OR 1.06, 95% CI 1.01-1.10), in particular, obesity hypoventilation syndrome (OR 3.7, 95% CI 1.2-11.1). CONCLUSION: The mean preoperative spirometry, lung volumes, and gas exchange values were within the established reference ranges. Restrictive ventilatory defects were less common than obstructive ventilatory patterns and were most prominently associated with obesity hypoventilation syndrome.

Changes in arterial oxygenation and self-reported oxygen use after lung volume reduction surgery.

RATIONALE: Lung volume reduction surgery (LVRS) is inconsistently reported to improve arterial oxygenation in patients with chronic obstructive pulmonary disease. OBJECTIVES: We studied the effects of surgery on oxygenation in a large cohort and identified predictors of postoperative oxygenation improvement. METHODS: We evaluated oxygenation in 1,078 subjects with chronic obstructive pulmonary disease enrolled in the National Emphysema Treatment Trial after LVRS compared with medical control subjects, including arterial blood gases, use of supplemental oxygen during treadmill walking, and self-reported use of oxygen during rest, exertion, and sleep. MEASUREMENTS AND MAIN RESULTS: Pa(O(2)) breathing room air was equal in medical and surgical subjects at baseline (64.8 vs. 65.0 mm Hg, P = not significant), but lower in medical subjects at 6 months (63.6 vs. 70.0 mm Hg, P < 0.001), 12 months (63.9 vs. 68.7 mm Hg, P < 0.001), and 24 months (62.4 vs. 68.0 mm Hg, P < 0.001). Fewer medical subjects required oxygen for treadmill walking at baseline compared with surgical subjects (46 vs. 53%, P = 0.02). However, more medical subjects required oxygen for this activity at 6 months (49 vs. 33%, P < 0.001), 12 months (50 vs. 36%, P < 0.001), and 24 months (52 vs. 42%, P = 0.02). Self-reported oxygen use was greater in medical than in surgical subjects at 6, 12, and 24 months. Multivariate modeling of preoperative characteristics showed baseline oxygenation status was the best predictor of postoperative oxygenation. CONCLUSIONS: LVRS increases Pa(O(2)), and decreases treadmill and self-reported use of oxygen for up to 24 months post-procedure. Clinical trial registered with www.clinicaltrials.gov (NCT 00000606).

Sex, depression, and risk of hospitalization and mortality in chronic obstructive pulmonary disease.

BACKGROUND: We sought to determine whether depressive or anxiety symptoms are associated with chronic obstructive pulmonary disease (COPD) hospitalization or mortality. These data were collected as part of the National Emphysema Treatment Trial (NETT), a randomized controlled trial of lung volume reduction surgery vs continued medical treatment conducted at 17 clinics across the United States between January 29, 1998, and July 31, 2002. METHODS: Prospective cohort study among participants in the NETT with emphysema and severe airflow limitation who were randomized to medical therapy. Primary outcomes were 1- and 3-year mortality, as well as COPD or respiratory-related hospitalization or emergency department visit during the 1-year follow-up period. Of 610 patients randomized to medical therapy, complete data on hospitalization and mortality were available for 3 years of follow-up for 603 patients (98.9%). RESULTS: Depressive symptoms were assessed using the Beck Depression Inventory (BDI) questionnaire, and anxiety was assessed using the State-Trait Anxiety Inventory. Among 610 subjects, 40.8% had at least mild to moderate depressive symptoms. Patients in the highest quintile of BDI score (BDI score, >or=15) had an increased risk of respiratory hospitalization in unadjusted analysis compared with patients in the lowest quintile (BDI score, < 5) (odds ratio [OR], 2.26; 95% confidence interval [CI], 1.30-3.93). After adjustment for disease severity, this relationship was no longer statistically significant. The adjusted risk of 3-year mortality was increased among those in the highest quintile of BDI score (OR, 2.74; 95% CI, 1.42-5.29) compared with those in the lowest quintile. Anxiety was not associated with hospitalization or mortality in this population. CONCLUSIONS: Depressive symptoms are common in patients with severe COPD and are treated in few subjects. Depressive symptoms are associated with increased risk for 3-year mortality but not 1-year mortality or hospitalization.

Genetic determinants of emphysema distribution in the national emphysema treatment trial.

RATIONALE: Computed tomography (CT) scanning of the lung may reduce phenotypic heterogeneity in defining subjects with chronic obstructive pulmonary disease (COPD), and allow identification of genetic determinants of emphysema severity and distribution. OBJECTIVES: We sought to identify genes associated with CT scan distribution of emphysema in individuals without alpha1-antitrypsin deficiency but with severe COPD. METHODS: We evaluated baseline CT densitometry phenotypes in 282 individuals with emphysema enrolled in the Genetics Ancillary Study of the National Emphysema Treatment Trial, and used regression models to identify genetic variants associated with emphysema distribution. MEASUREMENTS AND MAIN RESULTS: Emphysema distribution was assessed by two methods--assessment by radiologists and by computerized density mask quantitation, using a threshold of -950 Hounsfield units. A total of 77 polymorphisms in 20 candidate genes were analyzed for association with distribution of emphysema. GSTP1, EPHX1, and MMP1 polymorphisms were associated with the densitometric, apical-predominant distribution of emphysema (p value range = 0.001-0.050). When an apical-predominant phenotype was defined by the radiologist scoring method, GSTP1 and EPHX1 single-nucleotide polymorphisms were found to be significantly associated. In a case-control analysis of COPD susceptibility limited to cases with densitometric upper-lobe-predominant cases, the EPHX1 His139Arg single-nucleotide polymorphism was associated with COPD (p = 0.005). CONCLUSIONS: Apical and basal emphysematous destruction appears to be influenced by different genes. Polymorphisms in the xenobiotic enzymes, GSTP1 and EPHX1, are associated with apical-predominant emphysema. Altered detoxification of cigarette smoke metabolites may contribute to emphysema distribution, and these findings may lead to further insight into genetic determinants of emphysema.

Noninvasive positive pressure ventilation in critical and palliative care settings: understanding the goals of therapy.

OBJECTIVE: Although noninvasive positive pressure ventilation (NPPV) is a widely accepted treatment for some patients with acute respiratory failure, the use of NPPV in patients who have decided to forego endotracheal intubation is controversial. Therefore, the Society of Critical Care Medicine charged this Task Force with developing an approach for considering use of NPPV for patients who choose to forego endotracheal intubation. DATA SOURCES AND METHODS: The Task Force met in person once, by conference call twice, and wrote this document during six subsequent months. We reviewed English-language literature on NPPV for acute respiratory failure. SYNTHESIS AND OVERVIEW: The use of NPPV for patients with acute respiratory failure can be classified into three categories: 1) NPPV as life support with no preset limitations on life-sustaining treatments, 2) NPPV as life support when patients and families have decided to forego endotracheal intubation, and 3) NPPV as a palliative measure when patients and families have chosen to forego all life support, receiving comfort measures only. For each category, we reviewed the rationale and evidence for NPPV, key points to communicate to patients and families, determinants of success and failure, appropriate healthcare settings, and alternative approaches if NPPV fails to achieve the original goals. CONCLUSIONS: This Task Force suggests an approach to use of NPPV for patients and families who choose to forego endotracheal intubation. NPPV should be applied after careful discussion of the goals of care, with explicit parameters for success and failure, by experienced personnel, and in appropriate healthcare settings. Future studies are needed to evaluate the clinical outcomes of using NPPV for patients who choose to forego endotracheal intubation and to examine the perspectives of patients, families, and clinicians on use of NPPV in these contexts.

Surgical options for patients with COPD: sorting out the choices.

Surgical procedures designed to improve pulmonary function and quality of life of patients with advanced emphysema have been attempted for more than a century. Of the many attempted procedures, only giant bullectomy, lung transplantation, and lung-volume-reduction surgery have withstood the test of time and are currently being practiced. This article reviews each of these procedures and also develops a rational approach to selecting appropriate candidates for these 3 interventions.

Safety and efficacy of median sternotomy versus video-assisted thoracic surgery for lung volume reduction surgery.

BACKGROUND: The National Emphysema Treatment Trial, a randomized trial comparing lung volume reduction surgery with medical therapy for severe emphysema, included randomized and nonrandomized comparisons of the median sternotomy and video-assisted thoracoscopic approaches for lung volume reduction surgery. METHODS: Lung volume reduction surgery was performed by median sternotomy only at 8 centers and video-assisted thoracoscopy only at 3 centers; 6 centers randomized the approach to lung volume reduction surgery. Mortality, morbidity, functional status, and costs were assessed. RESULTS: In the nonrandomized comparison, 359 patients received lung volume reduction surgery by median sternotomy, and 152 patients received lung volume reduction surgery by video-assisted thoracoscopy. The 90-day mortality was 5.9% for median sternotomy and 4.6% for video-assisted thoracoscopy (P =.67). Overall mortality was 0.08 deaths per person-year for median sternotomy and 0.10 deaths per person-year for video-assisted thoracoscopy (video-assisted thoracoscopy-median sternotomy risk ratio, 1.18; P =.42). Complication rates were low and not statistically different for the 2 approaches. The median hospital length of stay was longer for median sternotomy than for video-assisted thoracoscopy (10 vs 9 days; P =.01). By 30 days after surgery, 70.5% of median sternotomy patients and 80.9% of video-assisted thoracoscopy patients were living independently (P =.02). Functional outcomes were similar for median sternotomy and video-assisted thoracoscopy at 12 and 24 months. Costs for the operation and the associated hospital stay and costs in the 6 months after surgery were both less for video-assisted thoracoscopy than for median sternotomy (P <.01 in both cases). Similar results were noted for the randomized comparison. CONCLUSIONS: Morbidity and mortality were comparable after lung volume reduction surgery by video-assisted thoracoscopy or median sternotomy, as were functional results. The video-assisted thoracoscopic approach to lung volume reduction surgery allowed earlier recovery at a lower cost than median sternotomy.

Surgical therapies for chronic obstructive pulmonary disease.

Surgical procedures for treating emphysema were first developed nearly 100 years ago. Despite a wide range of surgical procedures performed over the years, only three appear to have true clinical benefit: bullectomy, lung volume reduction surgery (LVRS), and lung transplantation. Lung volume reduction surgery has been reintroduced in the past decade and is currently under active research. A recent large, multicenter trial showed LVRS to improve quality of life, exercise capacity, and even survival in certain highly selected patients. Some individuals with emphysema may be candidates for either LVRS or lung transplantation. Patient-selection criteria for these procedures are being developed.