Radiographic Emphysema Research Articles

Pulmonary Function in HIV-Infected Recreational Drug Users in the Era of Anti-Retroviral Therapy.

Individuals with HIV infection commonly have pulmonary function abnormalities, including airflow obstruction and diffusion impairment, which may be more prevalent among recreational drug users. To date, the relationship between drug use and pulmonary function abnormalities among those with HIV remains unclear. To determine associations between recreational drug use and airflow obstruction, diffusion impairment, and radiographic emphysema in men and women with HIV. Cross-sectional analysis of pulmonary function and self-reported recreational drug use data from a cohort of 121 men and 63 women with HIV. Primary outcomes were the presence (yes/no) of: 1) airflow obstruction, (pre- or post-bronchodilator forced expiratory volume in 1 second/forced vital capacity<0.70); 2) moderate diffusion impairment (diffusing capacity for carbon monoxide <60% predicted); and 3) radiographic emphysema (>1% of lung voxels <-950 Hounsfield units). Exposures of interest were frequency of recreational drug use, recent (since last study visit) drug use, and any lifetime drug use. We used logistic regression to determine associations between recreational drug use and the primary outcomes. HIV-infected men and women reported recent recreational drug use at 56.0% and 31.0% of their study visits, respectively, and 48.8% of men and 39.7% of women reported drug use since their last study visit. Drug use was not associated with airway obstruction or radiographic emphysema in men or women. Recent crack cocaine use was independently associated with moderate diffusion impairment in women (odds ratio 17.6; 95% confidence interval 1.3-249.6, p=0.03). In this cross-sectional analysis, we found that recreational drug use was common among HIV-infected men and women and recent crack cocaine use was associated with moderate diffusion impairment in women. Given the increasing prevalence of HIV infection, any relationship between drug use and prevalence or severity of chronic pulmonary diseases could have a significant impact on HIV and chronic disease management.

Primary Lung Cancers Develop in Regions of Worse Radiographic Emphysema

SESSION TITLE: Decision-Making in Lung Cancer

Contributors to diffusion impairment in HIV-infected persons.

Abnormal diffusing capacity is common in HIV-infected individuals, including never smokers. Aetiologies for diffusing capacity impairment in HIV are not understood, particularly in those without a history of cigarette smoking. Our study was a cross-sectional analysis of 158 HIV-infected individuals without acute respiratory symptoms or infection with the aim to determine associations between a diffusing capacity of the lung for carbon monoxide (D(LCO)) % predicted and participant demographics, pulmonary spirometric measures (forced expiratory volume in 1 s (FEV1) and FEV1/forced vital capacity), radiographic emphysema (fraction of lung voxels < -950 Hounsfield units), pulmonary vascular/cardiovascular disease (echocardiographic tricuspid regurgitant jet velocity, N-terminal pro-brain natriuretic peptide) and airway inflammation (induced sputum cell counts), stratified by history of smoking. The mean D(LCO) was 65.9% predicted, and 55 (34.8%) participants had a significantly reduced D(LCO) (<60% predicted). Lower D(LCO) % predicted in ever-smokers was associated with lower post-bronchodilator FEV1 % predicted (p<0.001) and greater radiographic emphysema (p=0.001). In never-smokers, mean±SD D(LCO) was 72.7±13.4% predicted, and D(LCO) correlated with post-bronchodilator FEV1 (p=0.02), sputum neutrophils (p=0.03) and sputum lymphocytes (p=0.009), but not radiographic emphysema. Airway obstruction, emphysema and inflammation influence D(LCO) in HIV. Never-smokers may have a unique phenotype of diffusing capacity impairment. The interaction of multiple factors may account for the pervasive nature of diffusing capacity impairment in HIV infection.

Relationship Between Airflow Obstruction and Radiographic Emphysema and Clinical Follow-up of Subjects in a Lung Cancer Screening Progra

Relationship Between Airflow Obstruction and Radiographic Emphysema and Clinical Follow-up of Subjects in a Lung Cancer Screening Progra

Does radiographic emphysema correlate with low bone mineral density?

Several large epidemiologic studies have shown an association between chronic obstructive pulmonary disease (COPD) and osteoporosis. Recent studies have further implied an emphysema-specific association with low bone mineral density independent of obstruction severity. This review will outline the studies demonstrating an independent association between radiographic emphysema and decreased bone mineral density and will discuss potential disease mechanisms, including systemic inflammation and immune-mediated factors, linking these disease processes. Radiographic emphysema should be considered an independent risk factor in studies examining the mechanisms underlying COPD-related bone loss. Future research focused on the relationship between emphysema and low bone mineral density could provide mechanistic insight and result in the development of targeted therapies designed to halt progression of both disease processes.

Cross-sectional analysis of the utility of pulmonary function tests in predicting emphysema in ever-smokers.

Emphysema is largely an under-diagnosed medical condition that can exist in smokers in the absence of airway obstruction. We aimed to determine the sensitivity and specificity of pulmonary function tests (PFTs) in assessing emphysema using quantitative CT scans as the reference standard. We enrolled 224 ever-smokers (current or former) over the age of 40. CT of thorax was used to quantify the low attenuation area (% emphysema), and to measure the standardized airway wall thickness. PFTs were used individually and in combination to predict their ability to discriminate radiographic emphysema. Significant emphysema (>7%) was detected in 122 (54%) subjects. Twenty six (21%) emphysema subjects had no evidence of airflow obstruction (FEV1/FVC ratio <70%), while all subjects with >23% emphysema showed airflow obstruction. The sensitivity and specificity of spirometry for detecting radiographic emphysema were 79% and 75%, respectively. Standardized airway wall thickness was increased in subjects with airflow obstruction, but did not correlate with emphysema severity. In this cohort of lifetime ever-smokers, PFTs alone were inadequate for diagnosing emphysema. Airway wall thickness quantified by CT morphometry was associated with airflow limitation, but not with emphysema indicating that the heterogeneous nature of lung disease in smokers may represent distinct phenotypes.

Abstract CN07-04: Neutrophil elastase as a chemopreventive target for lung cancer

Abstract When combined, lung cancer and chronic obstructive pulmonary disease (COPD) account for &amp;gt;260,000 American deaths each year. Although the link between declining FEV1 and increased lung cancer incidence was identified over 20 years ago, the responsible mechanisms have not been deciphered. Two independent studies have recently demonstrated that it is the presence of emphysema, and not airflow obstruction, that is responsible for the increased risk of lung cancer in COPD patients. Emphysema, unlike COPD, has a strict anatomic definition: permanent enlargement of the peripheral airspaces distal to the terminal bronchioles. The prevailing theory regarding the pathogenesis of emphysema remains the proteinase:antiproteinase hypothesis. Inflammatory cells and inflammatory cell-derived proteinases are recruited to the lung upon chronic cigarette smoke exposure. When the proteinase burden exceeds the host's antiproteinase capacity, lung matrix tissue is destroyed and, in the absence of repair, emphysema results. When proteinase vs. antiproteinase activity is balanced, tissue homeostasis persists. We propose that the presence of radiographic emphysema on CT scan, which confers increased lung cancer risk, represents a case where the proteinase burden has surpassed the protective capability of the antiproteinase shield. As such, patient's displaying radiographic emphysema represent a group at increased risk for lung cancer, and therefore amenable to a chemopreventative strategy, especially one that would address a target common to both emphysema and lung cancer. We propose that that neutrophil-derived proteinase, neutrophil elastase (NE), is a viable chemopreventive target in COPD patients at risk for lung cancer. A role for this elastolytic enzyme in the pathogenesis of emphysema has been clearly established in both mouse and human studies. The presence of severe emphysema in A1AT deficient subjects has been attributed to uncontrolled NE activity, and is universally accepted as the pathogenic mechanism. Although previously unstudied, we have recently shown that NE promotes lung tumor growth in vivo (Nature Medicine 2010, 16:219-223). The mechanism by which NE promotes tumor growth represents an entirely new means by which a secreted proteinase can impact tumor behavior. NE is released near the tumor cell surface where it is internalized into tumor endosomes. NE degrades a target substrate, insulin receptor substrate-1 (IRS-1), within these tumor endosomes, which ultimately leads to PI3K activation and tumor cell proliferation. We propose that subjects displaying radiographic emphysema possess excessive proteinase burden, and therefore, increased NE activity. When lung cancers arise in these subjects, they will arise within a tumor microenvironment enriched for NE activity, and thus these cancers will display increased growth rates. Additional clinical studies are underway to establish NE as a bona fide therapeutic target for lung cancers arising in emphysematous subjects. Citation Information: Cancer Prev Res 2010;3(12 Suppl):CN07-04.

Abstract LB-210: A multiplexed serum biomarker immunoassay panel discriminates clinical lung cancer patients from cancer-free high-risk subjects in a CT-screened cohort

Abstract Clinical decision making in the setting of CT screening could benefit from accessible biomarkers that help predict the level of lung cancer risk in high-risk subjects with indeterminate pulmonary nodules commonly found by screening. The specificity and sensitivity needed to improve interpretation of CT images in the setting of a suspicious pulmonary nodule would be less stringent than those needed for lung cancer screening in the general population. As a first step in identifying and characterizing serum protein biomarkers to more accurately identify individuals with lung cancer in populations of high-risk tobacco-exposed individuals, we measured 70 cancer-related proteins by Luminex xMAP® multiplexed immunoassays in a training set of sera from 56 patients with biopsy-proven primary lung cancer diagnosed in a clinical setting and sera from 56 age-, sex- and smoking-matched CT-screened controls. These controls are drawn from a cohort of participants in the Pittsburgh Lung Screening Study (PLuSS) who have undergone CT screening and are known to be cancer-free after a minimum of 3 years follow-up. We found a profile of 8 biomarkers - PRL, TTR, THSP, SELE, CCL5, MIF, and SERPINE1 and ERBB2 - that distinguished lung cancer from controls in the training set with a sensitivity (SN) of 92.9% and specificity (SP) of 87.5%. The balanced accuracy (average of SN and SP) from 20-fold internal cross-validation of the training set was 82.5% ± 4.8%. We then applied this 8 biomarker model to an independent test set of 10 additional clinically detected lung cancer cases and 83 randomly selected PLuSS participants who were known to be cancer-free. These PLuSS controls in the test set included subjects with and without CT-detected pulmonary nodules and a range of airflow obstruction and radiographic emphysema. The biomarker model classified these test set cases and controls with a balanced accuracy of 83.6% (90.0% SN and 77.1% SP). Importantly, the misclassified PLuSS controls in the test set displayed no significant association with airway function variables or level of suspicion of pulmonary nodule. Taken together, these data suggest that the 8 biomarker panel classified lung cancer independently of pulmonary function abnormalities and the presence of non-cancerous pulmonary nodules, and thus may provide clinical utility in ruling out lung cancer in tobacco-exposed individuals screened by CT imaging. [Supported by NCI SPORE in Lung Cancer P50 CA090440 (JMS) and NCI Early Detection Research Network Biomarker Discovery Laboratory U01 CA084968 (WLB)]. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-210.

Association of Radiographic Emphysema and Airflow Obstruction with Lung Cancer

Association of Radiographic Emphysema and Airflow Obstruction with Lung Cancer

Quantification of single-breath underestimation of lung volume in emphysema

The extent to which a single breath measurement represents available gas dilutional as well as compressible thoracic volume in emphysema patients has not been quantified. We therefore measured single breath (TLCSB) and rebreathe helium dilution (TLCRB), and plethysmographic lung volume (TLCpleth), in fifty-five outpatients with clinical and radiographic emphysema, and in twenty-one normal controls. Among emphysema patients, TLCSB increasingly underestimated both TLCpleth and TLCRB as FEV1% predicted decreased (p for interaction=0.001 for both) by a mean of 1.7 l for TLCRB (p<0.001) and 2.2l for TLCpleth (p<0.001). In contrast, TLCRB underestimated TLCpleth by a mean of 0.5l (p<0.001) regardless of FEV1% (p for interaction=0.25). TLCSB, TLCRB, and TLCpleth showed strong agreement among normal subjects. We conclude that TLCSB underestimates available gas dilutional and compressible lung volume as physiologic emphysema severity increases. In contrast, TLCRB and TLCpleth show closer agreement which is unaffected by physiologic emphysema severity.

Emphysema and Airway Obstruction as Risk Factors for Lung Cancer

We read with great interest the article by Dr. Wilson and colleagues entitled ‘‘Association of Radiographic Emphysema and Airflow Obstruction with Lung Cancer’’ (1). Regarding the relationship between emphysema and risk of lung cancer, we are delighted that this work reproduces the results previously published by our group, thus validating their significance (2). There are a few comments we would like to make about this important study. First, although we acknowledge the differences in the study populations (age, smoking history and status, and clinical characterization), the higher prevalence of emphysema (47%) and chronic obstructive pulmonary disease (COPD) (47%) in comparison to our cohort is somewhat surprising. The higher prevalence of emphysema may be explained by the age (older) and smoking history (greater) of Wilson and coworkers’ population. Perhaps the higher prevalence of COPD is due to the fact that in their study, Wilson and coworkers performed spirometry without bronchodilator to diagnose and grade COPD. Lack of use of bronchodilators has elsewhere been associated with overdiagnosis of COPD in as many as 33% of individuals (3). In Wilson and coworkers’ group, many individuals may not have COPD according to current defining criteria, and many others may have less severe COPD, both of which results could seriously influence the statistical analysis. We wonder whether a correct diagnosis of COPD by post-bronchodilator spirometry would also result in a negative association between airway obstruction and risk of lung cancer, as we found in our cohort. Second, we encourage the authors to analyze the association between the pathologic characterization of the 99 lung cancers diagnosed in their cohort and the presence of emphysema. In our study, emphysema was associated more commonly with adenocarcinoma, and the tumors were located in the emphysematous areas in the majority of patients. Finally, we feel that a more detailed description of the protocol for the diagnosis of lung cancer in this screening trial is warranted. We find that the drop in compliance to 25% by the third year is quite striking. In spite of these discrepancies, we believe that studies such as Wilson and coworkers’ and the one published by our group underline the importance of the relationship between two of the most common and deadly diseases among smokers.

Association of Radiographic Emphysema and Airflow Obstruction with Lung Cancer

To study the relationship between emphysema and/or airflow obstruction and lung cancer in a high-risk population. We studied lung cancer related to radiographic emphysema and spirometric airflow obstruction in tobacco-exposed persons who were screened for lung cancer using chest computed tomography (CT). Subjects completed questionnaires, spirometry, and low-dose helical chest CT. CT scans were scored for emphysema based on National Emphysema Treatment Trial criteria. Multiple logistic regressions estimated the independent associations between various factors, including radiographic emphysema and airflow obstruction, and subsequent lung cancer diagnosis. Among 3,638 subjects, 57.5, 18.8, 14.6, and 9.1% had no, trace, mild, and moderate-severe emphysema, and 57.3, 13.6, 22.8, and 6.4% had no, mild (Global Initiative for Chronic Obstructive Lung Disease [GOLD] I), moderate (GOLD II), and severe (GOLD III-IV) airflow obstruction. Of 3,638 subjects, 99 (2.7%) received a lung cancer diagnosis. Adjusting for sex, age, years of cigarette smoking, and number of cigarettes smoked daily, logistic regression showed the expected lung cancer association with the presence of airflow obstruction (GOLD I-IV, odds ratio [OR], 2.09; 95% confidence interval [CI], 1.33-3.27). A second logistic regression showed lung cancer related to emphysema (OR, 3.56; 95% CI, 2.21-5.73). After additional adjustments for GOLD class, emphysema remained a strong and statistically significant factor related to lung cancer (OR, 3.14; 95% CI, 1.91-5.15). Emphysema on CT scan and airflow obstruction on spirometry are related to lung cancer in a high-risk population. Emphysema is independently related to lung cancer. Both radiographic emphysema and airflow obstruction should be considered when assessing lung cancer risk.

Do Radiographic Criteria for Emphysema Predict Physiologic Impairment?

The functional consequences of pulmonary emphysema have been estimated from autopsy studies. This antemortem study correlates structure as assessed by criteria applied to chest radiographs and function in earlier disease. Four thousand one hundred seven male shipyard and construction workers had chest radiographs scored for asbestosis using International Labour Office criteria and for emphysema using five criteria: hyperlucent lung fields, low flat diaphragms on posteroanterior views, low flat diaphragms on lateral radiographs, a wide retrosternal space, and bullae. Total lung capacity (TLC) was measured by planimetry of radiographs and forced vital capacity (FVC) and flows by spirometry: TLC minus FVC equaled residual volume (RV). All were expressed as percentage of predicted (% pred) adjusted for height, age, and duration of cigarette smoking. Linear regression modeling examined the influence of each emphysema criterion on function measurements. Four hundred three (10.1%) of 4,107 men had two or more emphysema criteria and 24.5% had asbestosis. Prevalence of 2 criteria varied by smoking status and was present in 20% of current smokers, 7.5% of ex-smokers, and 2% of never smokers. The TLC % pred and RV/TLC increased and % pred of FEV1/FVC and FEF25-75, FEV1, and FVC decreased with increasing radiographic emphysema criteria. Forty-four (10%) had normal results of spirometry with two or more radiographic emphysema criteria. Impairment of airway function worsened with each additional radiographic criteria of emphysema. These criteria were more strongly associated with an increase in RV/TLC than an increase in TLC.

Chronic lung disease in the Papua New Guinea Highlands.

In the Eastern Highlands of Papua New Guinea 46 men and 24 women with chronic lung disease underwent clinical and lung function investigations. In all cases the sole or predominant abnormality was irreversible airways obstruction, probably from chronic bronchitis with variable amounts of acompanying emphysema. There were close similarities to chronic obstructife lung disease in European populations in terms of symptoms, airways obstruction, transfer factor, and radiographic emphysema and inflammatory changes. Bronchiectasis and local fibrosis were present in a few subjects, but previous reports that pulmonary and pleural fibrosis are features of the disease were not confirmed. Possibly environmental and genetic factors may increase the associated blood gas disturbances leading to pulmonary hypertension. Unlike chronic obstructive lung disease in European populations, tobacco smoking is not an important aetiological factor. Although there is no direct evidence, the most likely possibilities are domestic wood smoke and acute chest infections.

Lower-zone emphysema in young patients without alpha1-antitrypsin deficiency.

Martelli, N. A., Goldman, E., and Roncoroni, A. J. (1974).Thorax, 29, 237-244. Lowerzone emphysema in young patients without α1-antitrypsin deficiency. Three young patients with radiographic pulmonary emphysema predominantly in the lower zones are reported. The clinical and physiological features were those observed in severe pulmonary emphysema. Predominance of the main lesions in the lower zones was confirmed in two cases by selective pulmonary angiography. One of the patients died and extensive panlobular emphysema was found at necropsy. Although the similarities between our patients and those with emphysema and α1-antitrypsin deficiency were remarkable, the latter condition was ruled out.

Prognosis in chronic obstructive pulmonary disease.

The results of pulmonary function tests in 663 patients and pulmonary vascular resistance in 136 patients were evaluated in relation to prognosis. The studies included spirogram, lung volumes, arterial blood gases, nitrogen washout, lung recoil at total lung capacity, airway resistance, diffusing capacity, and pulmonary vascular resistance. Forced expired volume in 1 second contributed significantly to predicting survival. Other tests probably contributed to predicting survival independent of 1-second forced expiratory volume. These tests were diffusing capacity for carbon monoxide, recoil pressure at total lung capacity, radiographic emphysema, arterial carbon dioxide tension, and single breath nitrogen washout. Decrease in 1-second forced expiratory volume averaged 52 ml per year. Changes from one follow-up period to another in any 1 patient showed considerable variability.

Treatment of experimental penicllin-resistant staphylococcal lesions with BRL 1241.

<h3>Abstract</h3> <h3>Background</h3> Patients with advanced lung disease who present with suspicious pulmonary nodules (SPNs) undergoing transthoracic needle aspiration pose a diagnostic challenge given risk for complications. Virtual bronchoscopic navigation (VBN) is an alternative means to biopsy patients. <h3>Study Design</h3> The study was a retrospective chart review of all patients who underwent VBN with the Archimedes platform. Demographic information, radiographic evidence of parenchymal lung disease and pulmonary function testing were gathered. Peri-procedure complications and clinical data on biopsy results were gathered to assist in determining both adequate tissue sample (defined if adequate specimen was obtained as per pathology/cytology report) and diagnostic yield (defined as if after further testing/CT imaging from 1 year post-procedure the diagnosis did not change). Univariate analysis was performed to determine the impact of clinical factors on diagnostic yield. <h3>Results</h3> Ninety-six patients with 110 nodules underwent VBN. Eight-eight patients (92%) had radiographic emphysema with 56% having moderate to severe. Fourteen patients (17%) had radiographic ILD. Adequate tissue sample at time of VBN was 93%. Overall diagnostic yield in 80 patients (excluding 16 patients who were initially benign/non-diagnostic that were lost to follow-up) was 72%. Overall complication rate was 7% with 1-pneumothorax (1%), 3-significant bleeding and 3-hospitalized for respiratory failure. <h3>Conclusion</h3> In our cohort of patients the diagnostic yield and complication rate were comparable to other studies where there were fewer patients with advanced lung disease. This data suggests that VBN-guided bronchoscopic biopsy of SPNs is a viable diagnostic option with an acceptable safety profile.