Rendell W. Ashton

Airway pressure release ventilation: an alternative mode of mechanical ventilation in acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS) results in collapse of alveoli and therefore poor oxygenation. In this article, we review airway pressure release ventilation (APRV), a mode of mechanical ventilation that may be useful when, owing to ARDS, areas of the lungs are collapsed and need to be reinflated (“recruited”), avoiding cyclic alveolar collapse and reopening. This mode may be useful in situations in which the lungs need to be recruited (reinflated) and held open.

State of the evidence: mechanical ventilation with PEEP in patients with cardiogenic shock

The need to provide invasive mechanical ventilatory support to patients with myocardial infarction and acute left heart failure is common. Despite the large number of patients requiring mechanical ventilation in this setting, there are remarkably few data addressing the ideal mode of respiratory support in such patients. Although there is near universal acceptance regarding the use of non-invasive positive pressure ventilation in patients with acute pulmonary oedema, there is more concern with invasive positive pressure ventilation owing to its more significant haemodynamic impact. Positive end-expiratory pressure (PEEP) is almost universally applied in mechanically ventilated patients due to benefits in gas exchange, recruitment of alveolar units, counterbalance of hydrostatic forces leading to pulmonary oedema and maintenance of airway patency. The limited available clinical data suggest that a moderate level of PEEP is safe to use in severe left ventricular (LV) dysfunction and cardiogenic shock, and may provide haemodynamic benefits as well in LV failure which exhibits afterload-sensitive physiology.

Strategies for Success in Fellowship

Internal Medicine subspecialty fellows across the continuum of their training should be aware of key strategies to gain the most out of their fellowship training. More than during any other time in a physician’s training, subspecialty fellows are expected to be proactive, self-motivated, and self-directed in their own education and career development. Training programs provide unique opportunities to individualize a fellow’s experiences with the goal of preparing each fellow for a specific career path. Identifying the optimal career path for a given fellow requires self-reflection and good mentoring. The successful launching of a career at the end of fellowship requires planning and time to ensure that individualized career-focused objectives and resources are provided during fellowship. Understanding key strategies for successful fellowship training is essential and can increase the likelihood of a successful and rewarding career.

Mounier-Kuhn Syndrome : Overcoming a Lack of Recognition

In 1897, Czyhlarz first described the finding of tracheobronchomegaly after noting the abnormality in an autopsy. Thirty-five years later, Mounier-Kuhn described the clinical presentation of cough with reduced effectiveness and large sputum production, with the radiographic appearance and bronchoscopic findings associated with enlarged major airways. The prevalence of the disease is not known, but is almost certainly underestimated, as a considerable number of cases remain subclinical and would only be recognized if seen incidentally on an imaging study. In addition, many clinicians have little knowledge of, or experience with the disease and may not recognize it even if imaging is performed. Even those physicians who are aware of the condition and identify it have only scant evidence on which to base their clinical management. They are forced to rely on the fewer than 100 case reports published in the literature to treat their patients. In this issue of the Southern Medical Journal, Menon and colleagues have published a case series of 8 patients with Mounier-Kuhn syndrome, defined as a tracheal and/or major bronchus diameter above the upper limit of normal. All the patients in their series presented with symptoms consistent with Mounier-Kuhn syndrome. The series fortifies the small amount of literature previously available on the condition, and importantly, provides a set of diagnostic criteria. Since there are effective therapeutic options available for Mounier-Kuhn syndrome, this contribution serves the pulmonary community well by raising the general awareness of the condition, suggesting a set of criteria for diagnosis and describing the common clinical presentations and complications of patients with the disease. As a clinical entity, Mounier-Kuhn syndrome presents some interesting features and challenges. The disease is more common in males and usually affects individuals in their third and fourth decades, although extremes of age have been reported. The diagnosis is made either radiographically or bronchoscopically. Genetic predisposition combined with environmental factors such as fume exposure have been proposed as the etiology of the disease, although no gene has been identified, and epidemiologic analysis is hampered by incomplete reporting and a lack of strict criteria for defining the diagnosis. The usual clinical presentation is that of chronic cough and sputum production with recurrent lower respiratory tract infections. The underlying defect is atrophy or even absence of elastic fibers and smooth muscle elements of the large airways. Diverticula may form between the cartilaginous rings of the trachea and main bronchi, which may in turn become colonized by bacteria and behave as a nidus for recurrent infection. As a result of inefficient cough and frequent infections, bronchiectasis may develop. Once the syndrome is recognized, management is primarily directed toward alleviating symptoms. Antibiotic therapy and bronchial hygiene remain the first line of treatment. In some cases, tracheobronchomalacia (weakness of the cartilaginous support of the large airways) may coexist with tracheobronchomegaly, leading to a dynamic collapse of the enlarged airways. In these cases, affected individuals may manifest a characteristic barking cough caused by turbulence in the collapsing airway. Intermittent positive pressure ventilation may play a role in the management, although it has not been systematically studied. Silicone and metallic stents have also been used with some success when conservative measures fail. Lung transplantation has also been proposed as a last resort for end-stage lung disease secondary to Mounier-Kuhn syndrome. Significant discrepancy in donor and recipient airway diameter is a surgical challenge. Furthermore, patients with a significant number of infected diverticula may continue to suffer from recurrent infections after transplantation. Despite its low incidence, Mounier-Kuhn syndrome can be a debilitating condition that occurs commonly enough to challenge physicians in a typical career, especially pulmonologists and thoracic surgeons. Long-term outcome reports are needed for the more aggressive treatment modalities including tracheobronchial stenting, positive airway ventilation and lung transplant. Reports such as that presented by Menon et al are important steps toward increased recognition of this syndrome, which hopefully will lead to improved outcomes for patients.

Fever and Dyspnea in a 61-Year-Old Woman With Metastatic Breast Cancer

A 61-year-old woman presented to her oncologist complaining of a 3-day history of fever, chills, fatigue, anorexia, and mild shortness of breath without cough or chest pain. She had recently received a diagnosis of invasive ductal carcinoma of the breast with liver metastases. She had completed her third cycle of palliative chemotherapy 3 weeks prior to presentation. Her chemotherapy regimen consisted of doxorubicin, cyclophosphamide, pegfilgrastim, dexamethasone (10 mg IV), and lorazepam. She also received oral dexamethasone, 4 mg twice daily for 3 days, after every cycle for nausea. Her medical history included hypertension, and she had recently quit smoking (40 pack-year smoking history). She denied contacts with sick persons, pets, travel, or history of malignancy among parents or siblings. She was admitted to the hospital and treated for community-acquired pneumonia without improvement. After 3 days, she required transfer to the ICU for worsening hypoxemia with persistent fever and leukocytosis.

Pirfenidone and Nintedanib for Treatment of Idiopathic Pulmonary Fibrosis.

Abstract Idiopathic pulmonary fibrosis is one of the most common entities of the family of disorders known as the interstitial lung diseases. It is a chronic, progressive, and often-fatal disease with a median survival time of 3 to 5 years. In 2014 the US Food and Drug Administration approved pirfenidone and nintedanib, two antifibrotic agents for the treatment of idiopathic pulmonary fibrosis. Because these are the only drugs approved that can alter the course of this rare but fatal disease, this article reviews the major studies that led to the approval of these drugs and examines the indications for treatment and the expected outcomes of therapy.

Hb Grove City [β38(C4)Thr→Ser, ACC>AGC; HBB: c.116C>G]: A New Low Oxygen Affinity β Chain Variant

A previously unreported β chain hemoglobin (Hb) variant, Hb Grove City [β38(C4)Thr→Ser, ACC>AGC; HBB: c.116C>G], was discovered in a woman who presented with hypoxia and mild anemia. Her young daughter also tested positive for the variant and displayed similar symptoms. Hemoglobin-oxygen dissociation testing confirmed right-shifted oxygen dissociation curves. A corresponding Hb variant was detected by high performance liquid chromatography (HPLC) and intact mass spectrometry (MS) but was not detected by capillary electrophoresis (CE), isoelectrofocusing (IEF) or alkaline or acid electrophoresis. DNA sequencing analysis confirmed a β-globin gene mutation. All three previous mutations at this locus affect oxygen affinity, as does this new variant. This newly described variant showed variable stability results and therefore may be mildly unstable but is not associated with microcytosis, significant hemolysis or clinically evident cyanosis. It is important to consider hemoglobinopathies in patients who are anemic and have unexplained hypoxia. Arterial blood gas and p50 evaluations may prevent unnecessary diagnostic interventions. Additionally, Hb variants with altered oxygen affinity can be electrophoretically silent; therefore, multiple methods including MS and/or DNA sequencing are warranted when clinical suspicion is high.

Inhaled therapy for acute COPD exacerbation in the hospital: are we missing the low-hanging fruit?

Divya C. Patel, DO and Rendell W. Ashton, MD In this issue of the Southern Medical Journal, Self and colleagues have published a retrospective study focused on patients hospitalized for acute nonYlife-threatening chronic obstructive pulmonary disease (COPD) exacerbations and the inhaled bronchodilator therapy prescribed during hospitalization. They examine the incidence of missed administration of inhaled medications and whether alternative means of administering these medications was utilized. They found that all patients were treated with nebulized short acting bronchodilators but approximately 21Y25% of scheduled treatments were not administered for various reasons. They also collected the documented reasons for missed doses and speculated about other potential reasons which may not have been documented, but the implications of this finding are striking and concerning. Most physicians would not be satisfied if they realized the medications they prescribed were only given to patients 75% of the time, and the question the authors raise from their finding is a good one: how canwe improve compliancewith prescribed bronchodilator therapy for our hospitalized patients? A big challenge to reliable nebulized medication administration in the hospital setting is the amount of time required for administration. Nebulized medications are time intensive and make compliance with scheduled doses difficult. The authors correctly point out that metered dose inhaler (MDI) delivery with a spacer is also an acceptable means of administering inhaled medications, and all available evidence suggests that in nearly every situation, it is just as effective as nebulizer delivery of the same medication. They conclude that more patients could and should be treated with MDI inhalers and that structured algorithms could help to effect this change. This proposal is a simple solution, but one that offers many potentially significant advantages to patients and possibly the healthcare system as well. COPD is a common condition which poses a substantial burden to our healthcare system, due in part to the hospitali zations, ICU admissions, and deaths from exacerbations. Much of what we have to offer has little or no proven benefit to mortality or survival. While we search for new therapies, we must use those therapies we do have as effectively as possible. With this in mind, if we can identify a way to improve compliance with inhaled bronchodilator therapy by up to 25% in the hospital setting, we should pursue it aggressively. An additional consideration in moving toward more use of MDI therapy in the hospital is the opportunity to teach patients proper inhaler technique. Many of us have had patients on good inhaled regimens admitted to the hospitalwith exacerbations, only to discover that the reason they failed treatment was that they were using their inhaler incorrectly. One likely benefit of increased use of MDIs in the hospital would be the chance to educate patients and observe their technique before they are discharged. In one study, the teaching time for using a MDI with a spacer in the emergency department was reported as a median of 6.5 minutes. The use of MDI would also have an economic impact. In a study byTurner et al, the cost of administering one 400-Kg dose of salbutamol by MDI was

Recurrent pneumonia in a 51-year-old woman due to congenital bronchoesophageal fistula.

1.73, while the cost of a 2.5-mg nebulized dose was

Smoking-Associated Interstitial Lung Diseases

2.62 (including the cost of medication, personnel wages, and equipment). In this study, the MDI was the least expensive method of administration for all levels of supervision if nebulized treatment took more than 4 minutes to administer. The questions now include whether compliance with prescribed inhaled medical regimens would indeed be improved by more frequent use of metered dose inhalers instead of nebulizers, and whether practitioners and patients outside of the research arena would accept the recommendation to switch to a different delivery method based on data running counter to longheld preconceptions about the superiority of nebulized therapy.