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. …

Pulmonary Vasculitides: A Review

Vasculitides are uncommon diseases that target multiple sites of the respiratory tract. Their manifestations vary widely, ranging from the banal (cough, rash) to life threatening (renal failure, diffuse alveolar hemorrhage). Small-vessel, antineutrophil cytoplasmic antibody–associated vasculitides are the principal forms affecting the lungs. Less often, larger vessel and immune-complex vasculitides afflict the respiratory tract, although the management of these conditions often mirrors that of the antineutrophil cytoplasmic antibody–associated vasculitides with immunosuppression and supplemental modalities such as plasma exchange. This paper reviews the epidemiology and clinical presentation of vasculitides with pulmonary involvement. The review also includes a pragmatic, evidence-based approach to management driven by disease severity. …

Rituximab in Connective Tissue Disease–associated Interstitial Lung Disease: A Community-based Experience and Review of Literature

Interstitial lung disease (ILD) is an important manifestation of the connective tissue disorders (CTD), which can lead to significant morbidity and mortality. Conventional therapy involves immunosuppression. Rituximab (RTX), a chimeric monoclonal antibody leading to B-cell depletion, appears to have some benefit in different forms of CTD-ILD. Our community-based, university-affiliated ILD clinic receives referrals from various medical practitioners in the community, including non-university based rheumatologists. The approach to the assessment and management of these patients is multidisciplinary and involves discussions with our center’s radiologists, pathologists (as applicable) and the referring rheumatologists (either university-affiliated or community-based). Therapy is initiated or changed in collaboration with the involved rheumatologists. Patients are followed clinically, functionally (using pulmonary function tests and 6-minute-walk testing), and radiologically using high-resolution chest computed tomography scans (HRCT). Among the patients referred to our clinic with CTD-ILD, six of them received RTX primarily for progressive pulmonary disease. The mean age was 51 years. All the patients were women. One patient had mixed connective tissue disease (MCTD), one patient had Sjögren’s syndrome, one patient had polymyositis, one patient had rheumatoid arthritis and two patients had antisynthetase syndrome. Among the six patients, community-based rheumatologists in private practice were managing four. Two patients received RTX prior to referral to our clinic. Four of the six patients demonstrated clinical improvement and stability in their lung function while on RTX. Three of the six patients demonstrated definite radiologic improvements. One patient developed anaphylactic symptoms and one patient developed a life-threatening infection. There is a growing body of medical…

Aspiration: /aspə’rāSH(ə)n/ Noun An Ambiguous Term Used for a Diagnosis of Uncertainty

Aspiration is a mechanism in which liquid or solid penetrates into the lungs, which overlaps several disease states. Use of the terms aspiration and aspiration pneumonia is ambiguous and may include pulmonary infection, oropharyngeal dysphagia, or gastroesophageal reflux disease. This article reviews the literature and classifies 13 distinct syndromes, grouped into 3 categories to help delineate the different disease states associated with pulmonary aspiration. Chronic anaerobic pulmonary infection should be most precisely referred to as anaerobic pneumonia. The commonly used term, aspiration pneumonia, is misleading to clinicians and should be abandoned. …

CAL02 Liposomes and Other Antitoxins: A New Generation of Anti-Infectives

While new generations of existing classes of antibiotics have predominated pipelines, novel nonantibiotic approaches such as antitoxins are gradually taking a more prominent position to address today’s most challenging issues in the field, notably the threatening rise of resistant strains and the unacceptably high rates of treatment failure and mortality despite the best of care. This review presents the clinical stage broad-spectrum antitoxin agent CAL02, which is active against both gram-positive and gram-negative bacteria including ESKAPE pathogens. CAL02 neutralizes bacterial pore-forming toxins, enzymes, and toxin-effector virulent appendages that play a vital and upstream role in pathogenic processes responsible for the progress and severity of infections such as severe pneumonia, bacteremia, and sepsis. The present overview underlines how combination therapies with antimicrobial agents operating in synergy with antibiotics, via unprecedented mechanisms of action, hold promise to dramatically improve standard of care and overturn the morbidity and mortality associated with resistant pathogens. The concerted efforts of academia, industry, clinicians, and regulatory agencies are contributing to a more accurate understanding of the various nontraditional approaches in development. Novel antitoxin treatments help reshape the antibiotic-driven set of mind. …

Monoclonal Antibody Therapy for Asthma

Asthma is characterized by airway inflammation and reversible airflow limitation. Severe asthma accounts for 5% to 10% of asthmatic patients but more than half of the cost of asthma care in the United States. There is increasing interest in characterizing and managing this difficult population. The mainstay of asthma treatment is the use of inhaled corticosteroids and bronchodilators, although in patients with severe asthma, many rely on systemic glucocorticoids for asthma control. Newer monoclonal antibodies are providing an alternative to systemic glucocorticoids for asthma control and exacerbation prevention. The first monoclonal antibody therapy approved for treatment of asthma was omalizumab, targeting IgE, a component of the allergic cascade. More recently, 2 monoclonal antibodies have been approved as add-on therapy for poorly controlled eosinophilic asthma. These target interleukin-5, a key cytokine in promoting eosinophil differentiation, survival, and recruitment. Another antibody targeting the interleukin-5 receptor on eosinophils is anticipating approval. Other monoclonal antibodies targeting a wide variety of intermediaries in the inflammatory cascade are under development. Evaluation of previously approved monoclonal antibodies that may have benefit in asthma is ongoing. An understanding of the pathophysiology of asthma and airway hyperreactivity, as well as use of biomarkers, will help clinicians appropriately target monoclonal antibody therapy to patients who are most likely to respond to these newer therapies. …

The Physiological Effect of High-flow Nasal Cannula

Synopsis: High-flow nasal cannula is superior to standard facemask oxygen for patients with acute hypoxic respiratory failure. A study by Tommaso Mauri and colleagues examines the physiological changes associated with high-flow nasal cannula, which may explain the unique benefits of this therapy. Source: Mauri T, Turrini C, Eronia N, et al. Physiologic effects of high-flow nasal cannula in acute hypoxemic respiratory failure. Am J Respir Crit Care Med. 2017;195(9):1207–1215. …