A case series describing common radiographic and pathologic patterns of hard metal pneumoconiosis.

INTRODUCTION: Hard metal pneumoconiosis is a rare but serious disease of the lungs associated with inhalational exposure to tungsten or cobalt dust. Little is known about the radiologic and pathologic characteristics of this disease and the efficacy of treating with immunosuppression. OBJECTIVE: We describe the largest cohort of patients with hard metal pneumoconiosis in the literature, including radiographic and pathologic patterns as well as treatment options. METHODS: We retrospectively identified patients from the University of Pittsburgh pathology registry between the years of 1985 and 2016. Experts in chest radiology and pulmonary pathology reviewed the cases for radiologic and pathologic patterns. RESULTS: We identified 23 patients with a pathologic pattern of hard metal pneumoconiosis. The most common radiographic findings were ground glass opacities (93%) and small nodules (64%). Of 20 surgical biopsies, 17 (85%) showed features of giant cell interstitial pneumonia. Most patients received systemic corticosteroids and/or steroid-sparing immunosuppression. CONCLUSIONS: Hard metal pneumoconiosis is characterized predominately by radiographic ground glass opacities and giant cell interstitial pneumonia on histopathology. Systemic corticosteroids and steroid-sparing immunosuppression are common treatment options.

Obesity and extent of emphysema depicted at CT.

AIM: To investigate the underlying relationship between obesity and the extent of emphysema depicted at CT. METHODS AND MATERIALS: A dataset of 477 CT examinations was retrospectively collected from a study of chronic obstructive pulmonary disease (COPD). The low attenuation areas (LAAs; ≤950 HU) of the lungs were identified. The extent of emphysema (denoted as %LAA) was defined as the percentage of LAA divided by the lung volume. The association between log-transformed %LAA and body mass index (BMI) adjusted for age, sex, the forced expiratory volume in one second as percent predicted value (FEV1% predicted), and smoking history (pack years) was assessed using multiple linear regression analysis. RESULTS: After adjusting for age, gender, smoking history, and FEV1% predicted, BMI was negatively associated with severe emphysema in patients with COPD. Specifically, one unit increase in BMI is associated with a 0.93-fold change (95% CI: 0.91-0.96, p<0.001) in %LAA; the estimated %LAA for males was 1.75 (95% CI: 1.36-2.26, p<0.001) times that of females; per 10% increase in FEV1% predicated is associated with a 0.72-fold change (95% CI: 0.69-0.76, p<0.001) in %LAA. CONCLUSION: Increasing obesity is negatively associated with severity of emphysema independent of gender, age, and smoking history.

The minimal important difference of exercise tests in severe COPD.

Our aim was to determine the minimal important difference (MID) for 6-min walk distance (6MWD) and maximal cycle exercise capacity (MCEC) in patients with severe chronic obstructive pulmonary disease (COPD). 1,218 patients enrolled in the National Emphysema Treatment Trial completed exercise tests before and after 4-6 weeks of pre-trial rehabilitation, and 6 months after randomisation to surgery or medical care. The St George's Respiratory Questionnaire (domain and total scores) and University of California San Diego Shortness of Breath Questionnaire (total score) served as anchors for anchor-based MID estimates. In order to calculate distribution-based estimates, we used the standard error of measurement, Cohen's effect size and the empirical rule effect size. Anchor-based estimates for the 6MWD were 18.9 m (95% CI 18.1-20.1 m), 24.2 m (95% CI 23.4-25.4 m), 24.6 m (95% CI 23.4-25.7 m) and 26.4 m (95% CI 25.4-27.4 m), which were similar to distribution-based MID estimates of 25.7, 26.8 and 30.6 m. For MCEC, anchor-based estimates for the MID were 2.2 W (95% CI 2.0-2.4 W), 3.2 W (95% CI 3.0-3.4 W), 3.2 W (95% CI 3.0-3.4 W) and 3.3 W (95% CI 3.0-3.5 W), while distribution-based estimates were 5.3 and 5.5 W. We suggest a MID of 26 ± 2 m for 6MWD and 4 ± 1 W for MCEC for patients with severe COPD.

Prevalence and clinical correlates of bronchoreversibility in severe emphysema.

Chronic obstructive pulmonary disease (COPD) exhibits airflow obstruction that is not fully reversible. The importance of bronchoreversibility remains controversial. We hypothesised that an emphysematous phenotype of COPD would be associated with decreased bronchoreversibility. 544 patients randomised to the medical arm of the National Emphysema Treatment Trial formed the study group. Participants underwent multiple measurements of bronchoreversibility on a mean of four sessions over 1.91 yrs. They were also characterised by measures of symptoms, quality of life and quantitative measures of emphysema by computed tomography. Mean baseline forced expiratory volume in 1 s (FEV(1)) in this patient population is 24% predicted. 22.2% of patients demonstrated bronchoreversibility on one or more occasions using American Thoracic Society/European Respiratory Society criteria. Few patients (0.37%) had bronchoreversibility on all completed tests. Patients who demonstrated bronchoreversibility were more likely to be male, and have better lung function and less emphysema. 64% of patients demonstrated large (> or =400 mL) changes in forced vital capacity (FVC). In a severe emphysema population, bronchoreversibility as defined by change in FEV(1) is infrequent, varies over time, and is more common in males and those with less severe emphysema. Improvements in FVC, however, were demonstrated in the majority of patients.

Selection of patients for lung volume reduction surgery using a power law analysis of the computed tomographic scan.

BACKGROUND: A study was undertaken to test the hypothesis that patients respond better to lung volume reduction surgery (LVRS) if their emphysema is confluent and predominantly located in the upper lobes. METHODS: A density mask analysis was used to identify voxels inflated beyond 10.2 ml gas/g tissue (-910 HU) on preoperative and postoperative CT scans from patients receiving LVRS. These hyperinflated regions were considered to represent emphysematous lesions. A power law analysis was used to determine the relationship between the number (K) and size (A) of the emphysematous lesions in the whole lung and two anatomical regions using the power law equation Y=KA(-D). RESULTS: The analysis showed a positive correlation between the change in the power law exponent (D) and the change in exercise (Watts) after surgery (r=0.47, p=0.03). There was also a negative correlation between the power law exponent D in the upper region of the lung preoperatively and the change in exercise following surgery (r=-0.60, p<0.05). CONCLUSIONS: These results confirm that patients with large upper lobe lesions respond better to LVRS than patients with small uniformly distributed disease. Power law analysis of lung CT scans provides a quantitative method for determining the extent and location of emphysema within the lungs of patients with COPD.

Core to rind distribution of severe emphysema predicts outcome of lung volume reduction surgery.

Computed tomography (CT) has shown that emphysema is more extensive in the inner (core) region than in the outer (rind) region of the lung. It has been suggested that the concentration of emphysematous lesions in the outer rind leads to a better outcome following lung volume reduction surgery (LVRS) because these regions tend to be more surgically accessible. The present study used a recently described, computer-based CT scan analysis to quantify severe emphysema (lung inflation > 10.2 ml gas/g tissue), mild/moderate emphysema (lung inflation = 10.2 to 6.0 ml gas/g tissue), and normal lung tissue (lung inflation < 6.0 ml gas/g tissue) present in the core and rind of the lung in 21 LVRS patients. The results show that the quantification of severe emphysema independently predicts change in maximal exercise response and FEV(1). We conclude that a greater extent of severe emphysema in the rind of the upper lung predicts greater benefit from LVRS because it identifies the lesions most accessible to removal by LVRS.

Amplification of inflammation in emphysema and its association with latent adenoviral infection.

This study examines the hypothesis that the cigarette smoke-induced inflammatory process is amplified in severe emphysema and explores the association of this response with latent adenoviral infection. Lung tissue from patients with similar smoking histories and either no (n = 7), mild (n = 7), or severe emphysema (n = 7) was obtained by lung resection. Numbers of polymorphonuclear cells (PMN), macrophages, B cells, CD4, CD8 lymphocytes, and eosinophils present in tissue and airspaces and of epithelial cells expressing adenoviral E1A protein were determined using quantitative techniques. Severe emphysema was associated with an absolute increase in the total number of inflammatory cells in the lung tissue and airspaces. The computed tomography (CT) determined extent of lung destruction was related to the number of cells/m(2) surface area by R(2) values that ranged from 0.858 (CD8 cells) to 0.483 (B cells) in the tissue and 0.630 (CD4 cells) to 0.198 (B cells) in the airspaces. These changes were associated with a 5- to 40-fold increase in the number of alveolar epithelial cells expressing adenoviral E1A protein in mild and severe disease, respectively. We conclude that cigarette smoke-induced lung inflammation is amplified in severe emphysema and that latent expression of the adenoviral E1A protein expressed by alveolar epithelial cells influenced this amplification process.

Preoperative severity of emphysema predictive of improvement after lung volume reduction surgery: use of CT morphometry.

STUDY OBJECTIVE: To determine how the volume and severity of emphysema measured by CT morphometry (CTM) before and after lung volume reduction surgery (LVRS) relates to the functional status of patients after LVRS. DESIGN: A histologically validated CT algorithm was used to quantify the volume and severity of emphysema in 35 patients before and after LVRS: total lung volume (TLV), normal lung volume (< 6.0 mL gas per gram of tissue), volume of mild/moderate emphysema (ME; 6.0 to 10.2 mL gas per gram of tissue), volume of severe emphysema (> 10.2 mL gas per gram of tissue), surface area/volume (SA/V; meters squared per milliliter), and surface area (SA; meters squared). Outcome parameters included maximal cardiopulmonary exercise (CPX) performance in 21 patients and routine pulmonary function in all patients. We hypothesized that baseline CTM parameters predict response to LVRS and that the change in these parameters may offer insight into mechanisms of improvement. PATIENTS AND INTERVENTION: Thirty-five patients with severe emphysema who had successful LVRS. RESULTS: The significant decrease in TLV following LVRS was entirely accounted for by a decrease in severe emphysema. The SA/V and the SA both increased significantly following LVRS. The change in maximal CPX in watts following surgery correlated significantly with baseline values of severe emphysema (r = 0.60), which was collinear with TLV, and SA/V. The change in diffusing capacity of the lung for carbon monoxide revealed a significant positive linear relationship with preoperative severe emphysema (r = 0.37) and a negative relationship with ME (r = -0.37). Change in watts revealed a strong relationship with changes in severe emphysema (r = -0.75) and weaker but significant relationships with change in TLV, ME, SA/V, and SA. Other measures of pulmonary function revealed significant albeit less dominant relationships with baseline CTM and change in these indexes. CONCLUSION: Using CTM, we have identified a close relationship between baseline severe emphysema, or change in severe emphysema, and the improvement in CPX after LVRS. These observations support a potential role of CTM in future clinical trials for predicting responders to LVRS and identifying mechanisms of improvement.

A randomized, prospective evaluation of noninvasive ventilation for acute respiratory failure.

We compared noninvasive positive-pressure ventilation (NPPV), using bilevel positive airway pressure, with usual medical care (UMC) in the therapy of patients with acute respiratory failure (ARF) in a prospective, randomized trial. Patients were subgrouped according to the disease leading to ARF (chronic obstructive pulmonary disease [COPD], a non-COPD-related pulmonary process, neuromuscular disease, and status postextubation), and were then randomized to NPPV or UMC. Thirty-two patients were evaluated in the NPPV group and 29 in the UMC group. The rate of endotracheal intubation (ETI) was significantly lower in the NPPV than in the UMC group (6.38 intubations versus 21.25 intubations per 100 ICU days, p = 0.002). Mortality rates in the intensive care unit (ICU) were similar for the two treatment groups (2.39 deaths versus 4.27 deaths per 100 ICU days, p = 0.21, NPPV versus UMC, respectively). Patients with hypoxemic ARF in the NPPV group had a significantly lower ETI rate than those in the UMC group (7.46 intubations versus 22.64 intubations per 100 ICU days, p = 0.026); a similar trend was noted for patients with hypercapnic ARF (5.41 intubations versus 18.52 intubations per 100 ICU days, p = 0.064, NPPV versus UMC, respectively). Patients with ARF in the non-COPD category had a lower rate of ETI with NPPV than with UMC (8.45 intubations versus 30.30 intubations per 100 ICU days, p = 0.01). Although the rate of ETI was lower among COPD patients receiving NPPV, this trend did not reach statistical significance (5.26 intubations versus 15.63 intubations per 100 ICU days, p = 0.12, NPPV versus UMC, respectively). In conclusion, NPPV with bilevel positive airway pressure reduces the rate of ETI in patients with ARF of various etiologies.

Results of multifield conformal radiation therapy of nonsmall-cell lung carcinoma using multileaf collimation beams.

A five-field conformal technique with three-dimensional radiation therapy treatment planning (3-DRTP) has been shown to permit better definition of the target volume for lung cancer, while minimizing the normal tissue volume receiving greater than 50% of the target dose. In an initial study to confirm the safety of conventional doses, we used the five-field conformal 3-DRTP technique. We then used the technique in a second study, enhancing the therapeutic index in a series of 42 patients, as well as to evaluate feasibility, survival outcome, and treatment toxicity. Forty-two consecutive patients with nonsmall-cell lung carcinoma (NSCLC) were evaluated during the years 1993-1997. The median age was 60 years (range 34-80). The median radiation therapy (RT) dose to the gross tumor volume was 6,300 cGy (range 5,000-6,840 cGy) delivered over 6 to 6.5 weeks in 180-275 cGy daily fractions, 5 days per week. There were three patients who received a split course treatment of 5,500 cGy in 20 fractions, delivering 275 cGy daily with a 2-week break built into the treatment course after 10 fractions. The stages of disease were II in 2%, IIIA in 40%, IIIB in 42.9%, and recurrent disease in 14.3% of the patients. The mean tumor volume was 324.14 cc (range 88.3-773.7 cc); 57.1% of the patients received combined chemoradiotherapy, while the others were treated with radiation therapy alone. Of the 42 patients, 7 were excluded from the final analysis because of diagnosis of distant metastasis during treatment. Two of the patients had their histology reinterpreted as being other than NSCLC, 2 patients did not complete RT at the time of analysis, and 1 patient voluntarily discontinued treatment because of progressive deterioration. Median follow-up was 11.2 months (range 3-32.5 months). Survival for patients with Stage III disease was 70.2% at 1 year and 51.5% at 2 years, with median survival not yet reached. Local control for the entire series was 23.3+/-11.4% at 2 years. However, for Stage III patients, local control was 50% at 1 year and 30% at 2 years. Patients who received concurrent chemotherapy had significantly improved survival (P = 0.002) and local control (P = 0.004), compared with RT alone. Late esophageal toxicity of > or =Grade 3 occurred in 14.1+/-9.3% of patients (3 of 20) receiving combined chemoradiotherapy, but in none of the 15 patients treated with RT alone. Pulmonary toxicity limited to Grades 1-2 occurred in 6.8% of the patients, and none developed > or =Grade 3 pulmonary toxicity. Patients with locally advanced NSCLC, who commonly have tumor volumes in excess of 200 cc, presenta challenge for adequate dose delivery without significant toxicity. Our five-field conformal 3-DRTP technique, which incorporates treatment planning by dose/volume histogram (DVH) was associated with minimal toxicity and may facilitate dose escalation to the gross tumor.

A quantification of the lung surface area in emphysema using computed tomography.

Quantitative analysis of computed tomography (CT) has been combined with a stereologically based histologic analysis of lung structure to assess regional lung inflation and the structural features of the lung parenchyma. In this study, CT measurements of lung inflation were compared with histologic estimates of surface area in order to develop prediction equations that allow lung surface to volume ratio and surface area to be predicted from an analysis of the CT scan. The results show that mild emphysema is associated with an increase in lung volume and a reduction in surface to volume ratio, whereas surface area and tissue weight were only decreased in severe disease. The CT predicted surface to volume ratio correlated with histology, and both predicted and measured surface areas correlated with the diffusing capacity. We conclude that this CT analysis can be used to monitor the progression of emphysematous lung destruction in individual patients, and to assess the impact of both surgical and medical treatments for emphysema.

Early and long-term functional outcomes following lung volume reduction surgery.

In the past 3 years, lung volume reduction surgery has become the most controversial topic in the clinical management of patients with emphysema. Although literature has added to the understanding of the procedure, many important issues remain unclear. This article emphasizes functional and basic physiologic changes that occur following lung volume reduction surgery in patients with emphysema.

Changes in lung volume and volume of emphysema after unilateral lung reduction surgery: analysis with CT lung densitometry.

PURPOSE: To evaluate changes in volume of the lungs and volume of emphysema after unilateral lung reduction surgery (ULRS) by using computed tomographic (CT) lung densitometry. MATERIALS AND METHODS: Twenty-eight patients underwent CT before and 3 months after ULRS. With use of a density mask software program and a three-dimensional graphics workstation, CT scans were analyzed to define the volume of the lungs and the volume of emphysema. Pre- and postoperative mean CT numbers were determined. RESULTS: After ULRS, the surgically reduced lung volume decreased 22%, and the intact opposite lung volume increased 4%. Emphysema in the surgically reduced lung decreased 14% and was unchanged in the intact opposite lung. Mean CT numbers in the surgically reduced lung increased 26 HU but were unchanged in the intact opposite lung. CONCLUSION: The effects of ULRS on each lung can be evaluated by using CT lung densitometry and a three-dimensional graphics workstation. ULRS reduces emphysema and lung volume in the surgically reduced lung without statistically significant worsening of contralateral emphysema at 3 months.

Role of lung reduction in lung transplant candidates with pulmonary emphysema.

BACKGROUND: The average waiting time for candidates for lung transplantation (LTx) with end-stage emphysema is 21 months with a 15% mortality. We hypothesized that lung reduction might offer an alternative to LTx. METHODS: Of 95 patients with end-stage emphysema evaluated by our LTx program, 45 were accepted for both lung reduction and LTx and 35 underwent lung reduction. RESULTS: All 35 patients survived lung reduction. Thirty patients had a follow-up of 3 months. There was a significant improvement (p < 0.05) of forced expiratory volume in 1 second (0.64 to 0.97 L), forced vital capacity (2.12 to 2.76 L), residual volume (5.62 to 4.26 L), maximum voluntary ventilation (28.1 to 38.5 L/min), 6-minute walk (904 to 1,012 feet), Borg dyspnea index (3.7 to 2.4), and arterial carbon dioxide tension (44.9 to 41.6 mm Hg). Twenty patients (66%) were removed from the LTx list due to their significant improvement (group A). Compared with the remaining 10 patients with 3 months of follow-up (group B), percent increase in forced expiratory volume in 1 second (70% in group A versus 27% in group B) and in forced vital capacity (41% group A versus 18% group B) and percent decrease in residual volume (26% group A versus 1.5% group B) were significantly better in group A (p < 0.01). Seven patients in group B were bridged to LTx; 6 of these patients (86%) had hypercarbia before lung reduction compared with 8 (40%) in group A (p < 0.05). All are alive after LTx: the forced expiratory volume in 1 second is 53% and the forced vital capacity is 64% of predicted. CONCLUSIONS: Lung reduction is safe and effective in selected LTx candidates with end-stage emphysema and has the potential to provide an alternative to LTx. Long-term follow-up is warranted to confirm these results.

The accuracy of pneumotachograph measurements during mechanical ventilation.

We hypothesized that differences between the conditions under which a pneumotachograph (PT) is calibrated and those during data collection might lead to large errors in measured flow and volume during mechanical ventilation. A Fleisch No. 1 and Fleisch No. 2 and a screen PT were connected to "ideal" tubing configurations that optimized flow characteristics, and to ventilator tubing with and without a Y-connector and endotracheal (ET) tube. Each PT was also evaluated after water had accumulated in its resistive element. Air was passed through each PT configuration, using both a continuous and a pulsatile flow pattern, and collected in a water-seal spirometer. "Measured" and "true" flow and volume were determined from the PT and the spirometer, respectively. Measured flow and volume were falsely low when the PT was adapted to ventilator tubing. Addition of a Y-connector and ET tube caused measured flow and volume to increase, and, in some cases the relationship between measured and true flow became nonlinear. Water accumulation in the PT did not lead to measurement errors. We conclude that when a PT is used during mechanical ventilation, tubing geometry must be identical during calibration and data collection, and that calibration should be performed over the entire range of relevant flows.

Thoracoscopic laser bullectomy: a prospective study with three-month results.

One hundred forty-one patients were prospectively enrolled in a study of contact-tip laser bullectomy at four institutions. Ninety-one have had both preoperative and postoperative testing at 3 months. Nonsmoking patients with disabling dyspnea at less than 50 yards and with a forced expiratory volume in 1 second of 35% or less were enrolled. Testing included formal pulmonary function tests, arterial blood gasses, computed tomographic scans, ventilation/perfusion scans, echocardiograms, electrocardiograms, 6-minute walk testing, transdiaphragmatic pressures, and quality of life and dyspnea index questionnaires. A modest 16% improvement was noted in forced expiratory volume in 1 second (0.69 to 0.80 L), and there was a 29% improvement in 6-minute walk distances (655.2 to 846.3 feet). Oxygen use was completely discontinued in 16%. Risk factors for mortality included age, 6-minute walk distances, low diffusing capacity for carbon monoxide, high carbon dioxide tension, and high base excess. Minor improvement was judged from the dyspnea index and the Medical Outcome Study Short Form-36. Preoperative predictors of good outcome included heterogeneous disease, lack of carbon dioxide retention, and no emaciation (weight < 40 kg). Comparison of our results with those in the literature suggests that the improvement seen with the contact neodymium:yttrium-aluminum-garnet laser is not as good as that provided by the stapled techniques for volume reduction.