Ayman O. Soubani

Frequency and type of epidermal growth factor receptor mutations in African Americans with non-small cell lung cancer

Background: Epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) predict response to tyrosine kinase inhibitors. Mutations occur more commonly in never smokers and East Asians, but there are conflicting reports on the frequency of EGFR mutations in tumors from African Americans. Methods: Tumors from 67 African American and 77 white participants in previous case-control studies of lung cancer were selected to determine EGFR mutational status. Mutation analysis was performed using the Sequenom mass array analyzer (Sequenom, San Diego, CA). Results: Overall, 13.9% of the study population carried an EGFR mutation. EGFR mutations occurred in 11.9% of tumors from African Americans compared with 15.6% in whites (p = 0.53). All mutations found in African Americans were deletions in exon 19. The majority of mutations were found in nonsmokers among both African Americans (7/8) and whites (8/12). Conclusion: These results indicate that African Americans with NSCLC harbor somatic EGFR mutations at a frequency similar to whites with NSCLC. Thus, clinicians should not use race as a clinical decision parameter for the use of EGFR-tyrosine kinase inhibitors.

Chronic Obstructive Lung Diseases and Risk of Non-small Cell Lung Cancer in Women

Introduction: The link between lung cancer and chronic obstructive lung diseases (COPD) has not been well studied in women even though lung cancer and COPD account for significant and growing morbidity and mortality among women. Methods: We evaluated the relationship between COPD and non-small cell lung cancer in a population-based case-control study of women and constructed a time course of chronic lung diseases in relation to onset of lung cancer. Five hundred sixty-two women aged 18 to 74, diagnosed with non-small cell lung cancer and 564 population-based controls matched on race and age participated. Multivariable unconditional logistic regression models were used to estimate risk associated with a history of COPD, chronic bronchitis, or emphysema. Results: Lung cancer risk increased significantly for white women with a history of COPD (odds ratios [OR] = 1.85; 95% confidence intervals [CI]: 1.21–2.81), but this was not seen in African American women. Risk associated with a history of chronic bronchitis was strongest when diagnosed at age 25 or earlier (OR = 2.35, 95% CI: 1.17–4.72); emphysema diagnosed within 9 years of lung cancer was also associated with substantial risk (OR = 6.36, 95% CI: 2.36–17.13). Race, pack-years of smoking, exposure to environmental tobacco smoke as an adult, childhood asthma, and exposure to asbestos were associated with a history of COPD among lung cancer cases. Conclusions: In women, COPD is associated with risk of lung cancer differentially by race. Untangling whether COPD is in the causal pathway or simply shares risk factors will require future studies to focus on specific COPD features, while exploring underlying genetic susceptibility to these diseases.

Aspergillus Lung Disease in Patients with Sarcoidosis: A Case Series and Review of the Literature

Chronic cavitary pulmonary aspergillosis (CCPA) has been associated with advanced lung diseases. Pulmonary sarcoidosis, a granulomatous inflammatory disorder, is associated with CCPA. We identified CCPA in 2% of cases in a large cohort of sarcoidosis patients. We found a lack of response to medical treatment and poor outcome in this subgroup.

Critical care considerations of hematopoietic stem cell transplantation.

Objective:To review the available clinical data on the critical care complications of hematopoietic stem cell transplantation (HSCT). Data Source:The MEDLINE database and references from the identified articles related to the critical care in HSCT. Conclusion:HSCT is an important treatment for a variety of malignant and nonmalignant conditions. The procedure is, however, limited by significant complications that may involve every organ of the body. Up to 40% of HSCT recipients are admitted to the intensive care unit as a result of severe complications related to the transplantation. The outcome of those critically ill patients has been traditionally poor. However, recent advances in the transplantation procedure, diagnostic studies, antimicrobial prophylaxis and therapy, and intensive care unit care have improved the outcome of these patients. The increasing number of HSCTs performed annually, the unique complications that develop in these patients, and the improvement in the intensive care unit outcome make knowledge about the critical care aspect of HSCT an essential part of the current practice of critical care medicine.

An Update on Pulmonary Complications of Hematopoietic Stem Cell Transplantation

The indications for hematopoietic stem cell transplantation (HSCT) continue to expand. However, the risk for pulmonary complications post-HSCT continues to be high. Early recognition and treatment of pulmonary complications may improve outcomes. This is an overview of diagnosis, manifestations, and treatment of the most common infectious and noninfectious pulmonary complications post-HSCT. Knowing the patients timeframe post-HSCT (preengraftment, postengraftment, late), type of HSCT (allogeneic vs autologous), radiographic findings, and clinical presentation can help to differentiate between the many pulmonary complications. This article will also address pretransplantation evaluation and infectious and noninfectious complications in the patient post-HSCT. While mortality post-HSCT continues to improve, respiratory failure continues to be the leading cause of ICU admissions for patients who have undergone HSCT. Mechanical ventilation is a predictor of poor outcomes in these patients, and further research is needed regarding their critical care management, treatment options for noninfectious pulmonary complications, and mortality prediction models posttransplantation.

Clinical significance of lower respiratory tract Aspergillus culture in elderly hospitalized patients

In order to evaluate the clinical significance of Aspergillus-positive culture results from the lower respiratory tract specimens of elderly hospitalized patients, and to identify the clinical variables that differentiate between colonization and infection with Aspergillus spp. in this patient population, a retrospective study was conducted. The records of 66 elderly patients whose lower respiratory tract specimens yielded Aspergillus spp. between January 1995 and July 2000 were examined. The majority of the patients (n=61) were determined to be colonized with Aspergillus spp., and serious lung infection due to Aspergillus spp. was rare. Clinical, radiological, and microbiological data did not help differentiate between infection and colonization.

The Clinical and Radiologic Features of Nodular Pulmonary Sarcoidosis

Study Objectives Nodular sarcoidosis is an uncommon presentation of sarcoidosis. Our objective was to describe the clinical characteristics of a large cohort of patients with nodular sarcoidosis. Methods We performed a retrospective study of patients with nodular sarcoidosis diagnosed at an urban teaching hospital over a 10-year period. Results Thirty-three patients with nodular sarcoidosis were identified. All patients were African-American. The mean age was 35 and the female-to-male ratio was 5:1. Twenty-six patients were current or former smokers. All patients had chest CT scan and/or chest radiograph evidence of pulmonary masses. Twenty-seven patients had multiple pulmonary masses/nodules and six had solitary pulmonary nodules/masses. The upper lobes were involved in 27 patients. Mediastinal lymphadenopathy and pleural-based masses were present in 30 and 20 patients, respectively. Extrapulmonary manifestations were present in 14 patients. All patients had tissue diagnosis of noncaseating granulomas with negative culture. Twenty-two patients underwent bronchoscopy with transbronchial biopsies, which were diagnostic in 19. Follow-up data were available on 27 patients: complete or nearly complete resolution of the pulmonary masses—either spontaneously or with systemic treatment—was documented for 19 patients, no change in the radiologic findings for 7 patients, and progression to pulmonary fibrosis for 1 patient. Conclusions Nodular sarcoidosis is a rare presentation of pulmonary sarcoidosis. It usually presents with multiple pulmonary masses that tend to be peripheral and are associated with mediastinal lymphadenopathy. Bronchoscopy with transbronchial biopsies has high diagnostic yield. Despite its ominous presentation, nodular sarcoidosis has favorable prognosis.

Nuclear, compared with combined nuclear and cytoplasmic expression of maspin, is linked in lung adenocarcinoma to reduced VEGF-A levels and in Stage I, improved survival

Aims:  To evaluate whether there is a correlation between the subcellular localization of maspin and the histological, molecular and biological features of pulmonary adenocarcinoma, particularly addressing the hypothesis that the tumour inhibitor properties of maspin may be linked to a nuclear, compared with a combined nuclear and cytoplasmic expression pattern.

The outcome of cancer patients with acute respiratory distress syndrome

OBJECTIVE The objective of the study is to determine the 28-day mortality of critically ill cancer patients with acute respiratory distress syndrome (ARDS). DESIGN This is a retrospective cohort study of patients enrolled in the ARDS Network randomized controlled trials. RESULTS A total of 2515 patients did not have cancer, and 116 patients had cancer. Patients with cancer were older (median, 61 vs 49 years; P < .0001), more critically ill (the median Acute Physiology and Chronic Health Evaluation III score without cancer comorbidity was 105 for the cancer group compared with 87 for those without cancer; P < 0.0001), and more likely to have pneumonia or sepsis as cause of acute lung injury (79.31% vs 62.70%; P = .0011). The overall mortality at day 28 was 25.7%. Patients with cancer had significantly higher mortality (55.2%) compared with those without cancer (24.3%) (P < .0001). The odds ratio for mortality from ARDS at 28 days for cancer patients was 2.54 (95% confidence interval [CI], 1.570-4.120). Acute Physiology and Chronic Health Evaluation III score and age were found to be significant predictors of outcome in cancer patients with odds ratio of 1.034 (95% CI, 1.007-1.062; P = .0135) and 1.075 (95% CI, 1.024-1.129, P = .0036), respectively. CONCLUSIONS Cancer patients with ARDS have a significantly higher risk of death compared with those without cancer. The increased risk appeared to be mediated by increased severity of illness at presentation, as well as by age.

The Outcome of Medical Intensive Care for Lung Cancer Patients: The Case for Optimism

In recent years, there have been significant advances in the management of patients with lung cancer. This progress is associated with increased use of medical intensive care units (ICUs) for the management of a variety of complications related to cancer, its treatment, or comorbid illnesses. At the same time, there are advances in the care of critically ill patients in general. Over the last decade, there are several studies that report progressive improvement in the outcome of lung cancer patients admitted to the medical ICUs. On average, the ICU and hospital mortality rates of lung cancer patients are 36% and 51%, respectively. These rates are approaching those of critically ill general population. However, it is clear that not all lung cancer patients will benefit from this aggressive care. Although there are no absolute predictors, the current evidence suggests that advanced refractory cancer, poor baseline performance status, the need for mechanical ventilation, and multiple organ system failures are factors associated with worse ICU outcome. Further studies are needed to better triage patients who are going to benefit from ICU care; determine the optimal duration of this care; and assess the impact of this therapy on the long-term survival, cancer treatment, and quality of life of these patients.