Augustine S. Lee

Pulmonary complications in bone marrow transplantation: a practical approach to diagnosis and treatment.

Pulmonary complications occur in 40% to 60% of recipients of bone marrow trans-plants, account for more than 90% of mortality, and develop during identifiable phases. Phase 1 (Days 1-30) includes pulmonary edema; diffuse alveolar hemorrhage; and various bacterial, fungal, and viral infections; Phase 2 (Days 31-100) usually requires a distinction between cytomegalovirus pneumonitis and idiopathic pneumonia syndrome; and Phase 3 (Day 100+) includes complications that are due to chronic graft-versus-host disease and associated bronchiolitis obliterans. The spectrum of pulmonary complications has been influenced by changes in transplantation technique, prophylactic treatment for infections, and the use of new chemotherapeutic agents that contribute to lung injury. Nonetheless, infections remain a leading cause of morbidity and mortality. The most serious complications result in respiratory failure, for which the prognosis has not improved significantly over the last 2 decades. In this article, we describe our algorithmic approach to the diagnosis and management of these complications.

The burden of idiopathic pulmonary fibrosis: An unmet public health need

Idiopathic pulmonary fibrosis (IPF) is a fibrotic lung disease of unknown cause characterized by relentlessly progressive restrictive-ventilatory limitation, hypoxia, dyspnea, and cough. Both the incidence and prevalence of IPF appears to be increasing, with little impact on its dismal 3-year median survival, despite two decades of clinical trials. Increasingly recognized are the serious associated comorbid illnesses, including pulmonary hypertension, chronic obstructive pulmonary disease, gastroesophageal reflux disease, obstructive sleep apnea, obesity, lung cancer, and depression that further contribute to the substantial rise in the use of IPF-related healthcare resources. At present, lung transplantation remains the sole viable treatment for the few who qualify. Pharmacologic interventions targeting lung function and survival have remained largely disappointing, and very few investigations have specifically targeted comorbid conditions, symptoms, quality-of-life, and healthcare resource utilization. In reviewing the burden of illness associated with IPF, including the epidemiology, comorbidities, quality-of-life and the physical, psychosocial, and economic costs of this devastating disease, we hope to highlight some of the unmet medical needs associated with IPF, and encourage both public support and further investigations into these and other patient-centered outcomes and not just that of survival and lung function.

Vertebral Aspergillus Osteomyelitis and Acute Diskitis in Patients With Chronic Obstructive Pulmonary Disease

Aspergillus osteomyelitis of the spine with acute diskitis has been well documented in immunocompromised hosts but is rare in immunocompetent patients. Predisposing factors to infection are prolonged neutropenia, hematologic malignancies, chemotherapy, history of prior spinal trauma or surgery, allograft transplantation, or any condition requiring the use of long-term immunosuppressive agents or systemic corticosteroids. Patients with chronic obstructive pulmonary disease (COPD) treated with systemic corticosteroids for either long-term management or frequent exacerbations are at potential risk for such infections. Patients with severe COPD treated primarily with inhaled corticosteroids are considered immunocompetent. This report describes 2 cases of Aspergillus osteomyelitis with acute diskitis in apparently immunocompetent patients with COPD who, aside from brief courses of systemic corticosteroids, were using inhaled corticosteroid therapy. One patient was treated with intravenous amphotericin B alone, whereas the other received amphotericin B and underwent surgical debridement. Both have done well and were symptom free at 6-month follow-up.

Respiratory disease and the oesophagus: reflux, reflexes and microaspiration

Gastro-oesophageal reflux is associated with a wide range of respiratory disorders, including asthma, isolated chronic cough, idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease and cystic fibrosis. Reflux can be substantial and reach the proximal margins of the oesophagus in some individuals with specific pulmonary diseases, suggesting that this association is more than a coincidence. Proximal oesophageal reflux in particular has led to concern that microaspiration might have an important, possibly even causal, role in respiratory disease. Interestingly, reflux is not always accompanied by typical reflux symptoms, such as heartburn and/or regurgitation, leading many clinicians to empirically treat for possible gastro-oesophageal reflux. Indeed, costs associated with use of acid suppressants in pulmonary disease far outweigh those in typical GERD, despite little evidence of therapeutic benefit in clinical trials. This Review comprehensively examines the possible mechanisms that might link pulmonary disease and oesophageal reflux, highlighting the gaps in current knowledge and limitations of previous research, and helping to shed light on the frequent failure of antireflux treatments in pulmonary disease.

Incidence and risk factors of recurrent acute lung injury

Objective:To determine risk factors for development of recurrent acute lung injury. Design:A population-based case-control study. Setting:The study was conducted in Olmsted County, MN, from 1999 to 2008. Patients:Using a validated electronic screening protocol, investigators identified intensive care patients with acute hypoxemia and bilateral pulmonary infiltrates. Interventions:None. Measurements and Main Results:The presence of acute lung injury was independently confirmed according to American-European Consensus Conference criteria. Recurrent acute lung injury cases were subsequently matched (1:1:1) with two controls (single acute lung injury and no acute lung injury) on age, gender, duration of follow-up, and predisposing conditions. Risk factors evaluated included gastroesophageal reflux disease, alcohol consumption, smoking, chronic opioid use, and transfusions. We identified 917 patients with acute lung injury, 19 of which developed a second episode, yielding a frequency of 2.02 (95% confidence interval 1.10–2.93) per 100,000 person years. The median time to development of the second episode was 264 days (interquartile range 80–460 days), with a mortality of 47% during the episode. The history of gastroesophageal reflux disease was highly prevalent in patients who developed recurrent acute lung injury: 15 of 19 patients (79%) compared to 5 of 19 (26%) matches with a single episode of acute lung injury (p = .006) and 8 of 19 (42%) matches without acute lung injury (p = .016). Other exposures were similar between the cases and the two matched controls. Conclusions:Recurrent acute lung injury is not a rare phenomenon in the intensive care unit and may continue to increase with improvements in survival following acute lung injury. Gastroesophageal reflux disease was identified as an important risk factor for recurrent acute lung injury and may suggest an important role of gastric aspiration in the development of this syndrome.

Prehospital Use of Inhaled Corticosteroids and Point Prevalence of Pneumonia at the Time of Hospital Admission: Secondary Analysis of a Multicenter Cohort Study

OBJECTIVE To address clinical concern regarding the use of inhaled corticosteroids (ICSs) and the risk for pneumonia, particularly among patients with chronic obstructive pulmonary disease (COPD) and asthma. PATIENTS AND METHODS A multicentered prospective cohort of patients admitted to the hospital from March 1, 2009, through August 31, 2009, with pneumonia or another risk factor for acute respiratory distress syndrome was analyzed to determine the risk for pneumonia requiring hospitalization among patients taking ICSs. The adjusted risk (odds ratio [OR]) for developing pneumonia because of ICSs was determined in a multiple logistic regression model. RESULTS Of the 5584 patients in the cohort, 495 (9%) were taking ICSs and 1234 (22%) had pneumonia requiring hospitalization. In univariate analyses, pneumonia occurred in 222 (45%) of the patients on ICSs vs 1012 (20%) in those who were not (OR, 3.28; 95% CI, 2.71-3.96; P<.001). After adjusting in the logistic regression model, prehospital ICS use was not significantly associated with pneumonia in the whole cohort (OR, 1.20; 95% CI, 0.93-1.53; P=.162), among the subset of 589 patients with COPD (OR, 1.40; 95% CI, 0.95-2.09; P=.093), among the 440 patients with asthma (OR, 1.07; 95% CI, 0.61-1.87; P=.81), nor among the remaining 4629 patients without COPD or asthma (OR, 1.32; 95% CI, 0.88-1.97; P=.179). CONCLUSION When adjusted for multiple confounding variables, ICS use was not substantially associated with an increased risk for pneumonia requiring admission in our cohort.

Airway Pepsin Levels in Otherwise Healthy Surgical Patients Receiving General Anesthesia With Endotracheal Intubation

BACKGROUND Airway pepsin has been increasingly used as a potentially sensitive and quantifiable biomarker for gastric-to-pulmonary aspiration, despite lack of validation in normal control subjects. This study attempts to define normal levels of airway pepsin in adults and distinguish between pepsin A (exclusive to stomach) and pepsin C (which can be expressed by pneumocytes). METHODS We performed a prospective study of 51 otherwise healthy adult patients undergoing elective extremity orthopedic surgery at a single tertiary-care academic medical center. Lower airway samples were obtained immediately following endotracheal intubation and just prior to extubation. Total pepsin and pepsin A concentrations were directly measured by an enzymatic activity assay, and pepsin C was subsequently derived. Pepsinogen/pepsin C was confirmed by Western blot analyses. Baseline characteristics were secondarily compared. RESULTS In all, 11 (22%; 95% CI = 9.9%-33%) had detectable airway pepsin concentrations. All 11 positive specimens had pepsin C, without any detectable pepsin A. Pepsinogen/pepsin C was confirmed by Western blot analyses. In a multivariate logistic regression, men were more likely to have airway pepsin (OR, 12.71, P = .029). CONCLUSIONS Enzymatically active pepsin C, but not the gastric-specific pepsin A, is frequently detected in the lower airways of patients who otherwise have no risk for aspiration. This suggests that nonspecific pepsin assays should be used and interpreted with caution as a biomarker of gastropulmonary aspiration, as pepsinogen C potentially expressed from pneumocytes may be detected in airway samples.

A prospective, comparative trial of standard and breath-actuated nebulizer: Efficacy, safety, and satisfaction

BACKGROUND: Nebulized drug delivery is a cornerstone of therapy for obstructive lung disease, but the ideal nebulizer design is uncertain. The breath-actuated nebulizer (BAN) may be superior to conventional nebulizers. This study compared the BAN to standard nebulizer with regard to efficacy, safety, and patient and respiratory therapist (RT) satisfaction. METHODS: Adults admitted to the hospital and for whom nebulizer therapy was prescribed were enrolled. Subjects were randomly assigned to either AeroEclipse II or standard nebulizer and were surveyed at the completion of each treatment. BAN delivered albuterol 2.5 mg or albuterol 2.5 mg plus ipratropium 0.25 mg. Standard nebulizer delivered albuterol 2.5 mg or albuterol plus ipratropium 0.5 mg. An RT assessed each subjects heart rate, respiratory rate, and peak expiratory flow rate prior to and following treatment. Treatment time and adverse events were recorded. Each RT was asked to assess his/her satisfaction with each of the nebulizers. RESULTS: Twenty-eight subjects were studied. The mean age was 69 years. Fifty-four percent of the subjects indicated that overall the BAN was superior to conventional nebulizer therapy; 68% indicated that duration was preferable with the BAN. RTs were more satisfied with the BAN, based on overall performance, treatment duration, and ease of use. There were no significant differences in heart rate, peak expiratory flow rate, or respiratory rate before or after nebulization therapy with either device. The duration of treatment was significantly lower with the BAN (4.1 min vs 9.9 min, P < .001). Additionally, the BAN was associated with a lower occurrence of adverse events. CONCLUSIONS: Patients and RTs expressed greater satisfaction with the BAN, compared with standard nebulizer. Pre- and post-treatment vital signs did not differ between groups, but use of the BAN was associated with a shorter duration and a lower occurrence of adverse events. Taken together, these data support the use of the BAN for nebulized medication delivery.

Weak peristalsis with large breaks in chronic cough: association with poor esophageal clearance

Gastroesophageal reflux plays an important role in chronic cough (CC). Whether disturbed esophageal motility contributes to increased esophageal reflux exposure or interferes with swallowed bolus clearance is unclear. This study used high resolution esophageal manometry and impedance (HRIM) together with Chicago Classification, and 24‐h impedance pH (MII/pH) to address these questions in patients with CC compared with heartburn (HB).

Accuracy of chest high-resolution computed tomography in diagnosing diffuse cystic lung diseases

The diffuse cystic lung diseases (DCLDs) are a group of pathophysiologically heterogeneous processes characterised by the presence of multiple, thin-walled, air-filled spaces within the pulmonary parenchyma [1]. The differential diagnosis of DCLDs includes lymphangioleiomyomatosis (LAM), follicular bronchiolitis (FB), lymphocytic interstitial pneumonia (LIP), Birt–Hogg–Dubé syndrome (BHD), pulmonary Langerhans cell histiocytosis (PLCH), amyloidosis, light chain deposition disease, cystic metastases, infectious entities such as Pneumocystis, and other aetiologies [2]. Bronchiectasis and bullous changes seen in chronic obstructive pulmonary disease can also produce high-resolution computed tomography (HRCT) patterns that mimic the DCLDs. Correct diagnosis of diffuse cystic lung diseases is established in most cases by critical review of HRCT features http://ow.ly/NvrCc