Efficacy of Dupilumab for Treatment of Moderate-to-Severe Asthma

Synopsis: Dupilumab is a novel biologic agent that targets the shared interleukin 4/13 receptor. It is safe and efficacious in patients with moderate-to-severe asthma; however, subgroup analysis suggests that patients with elevated markers of type-2 inflammation benefit most from this drug. Source: Castro M, Corren J, Pavord ID, et al. Dupilumab efficacy and safety in moderate-to-severe uncontrolled asthma. NEJM 2018;378:2486–2496. …

Zephyr Endobronchial Valves Improve FEV1 and Quality of Life in Heterogenous Emphysema

Synopsis: In patients with severe heterogenous emphysema and little or no collateral ventilation in target lobes, Zephyr Endobronchial Valve treatment provides statistical and clinical benefits in lung function and quality of life compared with current standard of care therapies over a 12-month period. Source: Criner GJ, Sue R, Wright S, et al. LIBERATE Study Group. A multicenter randomized controlled trial of Zephyr endobronchial valve treatment in heterogenous emphysema (LIBERATE). Am J Respir Crit Care Med 2018;198:1151–1164. …

Neurological Emergencies in the Intensive Care Unit

Neurological emergencies present a unique challenge in the intensive care unit, requiring rapid evaluation and treatment. There is a complex interplay in critically ill patients, wherein illness affects the brain and the brain can, in turn, affect the illness, making diagnosis and management challenging. In this review, we discuss the diagnosis and management of common neurological issues that may be encountered in the intensive care unit, including elevated intracranial pressure, traumatic brain injury, ischemic stroke, intracerebral hemorrhage, subarachnoid hemorrhage, status epilepticus, neurological complications of critical illness, neuromuscular respiratory failure, and neurological complications in the immunocompromised. …

Cough and Nasal Pain: Putting Together an Uncommon Diagnosis

The pulmonary vasculitides include a wide spectrum of disorders that have in common inflammation and destruction of pulmonary blood vessels. Granulomatosis with polyangiitis (GPA), formerly known as Wegener granulomatosis, is the most common of the antineutrophil cytoplasmic antibody–associated small-vessel vasculitides, and affects a number of organ systems. GPA affects a wide age range, although it typically presents in middle adulthood. The classic triad of GPA—upper airway involvement (sinusitis, otitis media, mucosal ulcerations, airway inflammation), lower respiratory tract disease, and glomerulonephritis—is not always evident at presentation. Furthermore, limited forms of GPA occur, in which the expected upper airway and renal involvement may be lacking. The imaging manifestations of GPA commonly include multiple, bilateral nodules or masses, frequently with cavitation or necrosis. Diffuse lung opacity due to alveolar hemorrhage, or tracheobronchial inflammation that may result in stenosis, may be encountered. Systemic GPA may be diagnosed when cytoplasmic antineutrophil cytoplasmic antibody/anti-proteinase 3 antibodies are detected in the proper clinical context, but, often, the diagnosis of GPA relies on recognition of a combination of common clinical, laboratory, and imaging findings with typical histopathologic changes noted from a biopsy of the affected tissue. A combination of a corticosteroid and immunomodulatory agents is used to induce and maintain remission in patients with GPA. Although potentially fatal if untreated, immunosuppressive therapy has dramatically improved survivorship in patients with GPA. …

Management of Pulmonary Vasculitis: A Concise Review

The pulmonary vasculitides are an uncommon group of disorders that are characterized by inflammation and necrosis of the blood vessel wall, usually involving the small and medium-sized blood vessels in the lung. Management has traditionally involved the use of immunosuppressive agents and newer adjunctive therapies such as plasmapheresis. Recent trials over the last decade have highlighted the successful use of these agents in treating this life-threatening illness; however, much remains unknown in terms of exact dosing of these agents and duration of treatment. Adverse events from these therapies remain a serious concern requiring close monitoring and a multidisciplinary approach. Other advances in this field include exploration of newer drugs, some of which are currently being used in randomized trials. This review is an update on the advances made in the management of pulmonary vasculitis over recent years, along with a suggested uniform approach to management based on disease severity classification. …

Bronchoscopy in the Immunosuppressed Patient

Bronchoscopy in the immunosuppressed patient is routinely undertaken, as mortality of immunosuppressed hosts with pulmonary infiltrates is high. Generally, complications from bronchoscopy are rare, with pneumothorax and respiratory failure being the most serious. Immunosuppressed hosts do not have a higher complication rate than the general patient. In patients with HIV, bronchoscopy should be undertaken even if sputum samples are negative when suspicion is high for Pneumocystis jirovecii or tuberculosis. Patients with a hematologic malignancy have a high incidence of pulmonary infiltrates, and delaying bronchoscopy can significantly reduce the diagnostic yield of a causative agent. Diagnostic testing should include galactomannan levels if the concern is high, even if serum testing is negative. Transbronchial biopsy does not increase the yield of an organism. In patients with stem cell and solid organ transplant, fungal and viral studies including galactomannan should be sent, and diffuse alveolar hemorrhage should be ruled out. Diagnostic bronchoscopy for pulmonary infiltrates in the immunosuppressed host is both a relatively safe and useful tool for increasing identification of an offending pathogen in the setting of a pulmonary infiltrate. Given the high morbidity and mortality associated with many of these disease processes, quick identification and pathology-directed treatment is necessary. Myth: Bronchoscopy in immunosuppressed patients for evaluation of pulmonary infiltrates is a high risk but high yield procedure. …

Extracorporeal Membrane Oxygenation for Acute Respiratory Distress Syndrome: The Doctors are In, but the Jury is Still Out

Despite attempts to optimize outcomes in acute respiratory distress syndrome (ARDS) using mechanical ventilation and medical management, the mortality associated with this syndrome remains very high. The use of extracorporeal membrane oxygenation (ECMO), particularly veno-venous ECMO (VV-ECMO), as a rescue therapy has grown significantly in recent decades. This review outlines the risks and benefits of ECMO for the treatment of ARDS, examines the body of evidence behind this practice, including 4 randomized controlled trials and 2 case-controlled studies, and discusses the remaining questions and directions for future research. Because VV-ECMO is far more frequently used in the treatment of ARDS than veno-arterial ECMO, referral to ECMO in this review will imply VV-ECMO unless specifically stated. …