ABSTRACT
Rationale: Small airway disease is an important pathophysiological feature of chronic obstructive pulmonary disease (COPD). Recently, "pre-COPD" has been put forward as a potential precursor stage of COPD that is defined by abnormal spirometry findings or significant emphysema on computed tomography (CT) in the absence of airflow obstruction. Objective: To determine the degree and nature of (small) airway disease in pre-COPD using microCT in a cohort of explant lobes/lungs. Methods: We collected whole lungs/lung lobes from patients with emphysematous pre-COPD (n = 10); Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage I (n = 6), II (n = 6), and III/IV (n = 7) COPD; and controls (n = 10), which were analyzed using CT and microCT. The degree of emphysema and the number and morphology of small airways were compared between groups, and further correlations were investigated with physiologic measures. Airway and parenchymal pathology was also validated with histopathology. Measurements and Main Results: The numbers of transitional bronchioles and terminal bronchioles per milliliter of lung were significantly lower in pre-COPD and GOLD stages I, II, and III/IV COPD compared with controls. In addition, the number of alveolar attachments of the transitional bronchioles and terminal bronchioles was also lower in pre-COPD and all COPD groups compared with controls. We did not find any differences between the pre-COPD and COPD groups in CT or microCT measures. The percentage of emphysema on CT showed the strongest correlation with the number of small airways in the COPD groups. Histopathology showed an increase in the mean chord length and a decrease in alveolar surface density in pre-COPD and all GOLD COPD stages compared with controls. Conclusions: Lungs of patients with emphysematous pre-COPD already show fewer small airways and airway remodeling even in the absence of physiologic airway obstruction.
Subject(s)
Asthma , Emphysema , Pulmonary Disease, Chronic Obstructive , Pulmonary Emphysema , Humans , Cross-Sectional Studies , Pulmonary Disease, Chronic Obstructive/complications , Pulmonary Disease, Chronic Obstructive/diagnostic imaging , Pulmonary Disease, Chronic Obstructive/pathology , Pulmonary Emphysema/complications , Pulmonary Emphysema/diagnostic imaging , Pulmonary Emphysema/pathology , Lung , Asthma/pathology , X-Ray MicrotomographyABSTRACT
Several oncogenic drivers have been identified in non-small cell lung cancer. Targeted therapies for these aberrations have already been successfully developed and implemented in clinical practice. Owing to improved sensitivity in genetic testing, more and more tumors with multiple driver mutations are identified, resulting in dilemmas for treating physicians whether and which targeted therapy to use. In this case series, we provide an overview of patients with intrinsic double mutations in oncogenic drivers and their reported response to targeted therapies, with a focus on epidermal growth factor receptor, anaplastic lymphoma kinase, cMET, and Kirsten rat sarcoma viral oncogene. We also include an unpublished case report on a patient with an epidermal growth factor receptor L858R and cMET exon 14 skipping.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/genetics , Lung Neoplasms/genetics , Mutation/genetics , Proto-Oncogene Proteins c-met/genetics , Anaplastic Lymphoma Kinase/genetics , Drug Resistance, Neoplasm/genetics , ErbB Receptors/genetics , Female , Genetic Testing , Humans , Middle Aged , Molecular Targeted Therapy , Neoplasm Metastasis , Proto-Oncogene Proteins p21(ras)/geneticsABSTRACT
BACKGROUND: Herpes simplex virus (HSV) is occasionally detected in the lower respiratory tract of patients in intensive care, but its clinical importance in such situations remains unclear. We did a prospective cohort study to define the prevalence, origin, risk factors, and clinical relevance of HSV in the respiratory tract of patients undergoing critical care. METHODS: We tested 764 patients admitted to intensive care for the presence of HSV in the respiratory tract, and assessed statistical relations between this virus and clinical variables. FINDINGS: HSV was detected by oropharyngeal swab in the upper respiratory tract of 169 (22%) of 764 patients, within 10 days of admission for 150 (89%) of these individuals. The virus was isolated in 58 (16%) of 361 patients whose lower respiratory tract was sampled. The presence of HSV in the throat was a risk factor for development of HSV infections in the lower respiratory tract (p<0.001). HSV was isolated most frequently in patients with severe disease. HSV in the throat was associated with acute respiratory distress syndrome (p<0.001) and with increased length of stay in intensive care (p<0.001). INTERPRETATION: Our data suggest that HSV reactivation or infection of the upper respiratory tract is frequent among patients in intensive care, and is a risk factor for development of lower respiratory tract infection with this virus, possibly by means of aspiration.