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.

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.

Lung reduction surgery in chronic obstructive lung disease.

In the 1960s the promise of the Brantigan lung reduction surgery was shattered when it was shown that the improvement in airway conductance drifted back towards the preoperative value over a period of 12 to 18 months. Since then there has been a marked improvement in our understanding of emphysema, its pathology, and techniques for obtaining images of the lung. In addition, reliable automated cardiopulmonary and physiologic testing, advances in critical care medicine, and new pharmacologic agents have improved patient care. Surgical techniques now allow better control of air leaks and access to anatomic regions not previously accessible. The combination of all of the above makes lung reduction surgery worth re-examining as a palliative procedure for severely symptomatic patients. Clearly, it is not a panacea but can in some cases produce dramatic improvements in symptomatology and quality of life. This article presents the available data describing potential mechanisms of improvement and clinical outcomes following lung reduction surgery. It also outlines areas that need further work, such as patient selection and surgical techniques.

Improvement in pulmonary function and elastic recoil after lung-reduction surgery for diffuse emphysema.

BACKGROUND: Pulmonary function may improve after surgical resection of the most severely affected lung tissue (lung-reduction surgery) in patients with diffuse emphysema. The basic mechanisms responsible for the improvement, however, are not known. METHODS: We studied 20 patients with diffuse emphysema before and at least three months after either a unilateral or a bilateral lung-reduction procedure. Clinical benefit was assessed by measurement of the six-minute walking distance and the transitional-dyspnea index, which is a subjective rating of the change from base line in functional impairment and the threshold for effort- and task- dependent dyspnea. Pressure-volume relations in the lungs were measured with static expiratory esophageal-balloon techniques, and right ventricular systolic function was assessed by echocardiography. RESULTS: The patients had significant improvement in the transitional-dyspnea index after surgery (P<0.001). The mean (+/-SD) coefficient of retraction, an indicator of elastic recoil of the lung, improved (from 1.3+/-0.6 cm of water per liter before surgery to 1.8+/-0.8 after, P<0.001). Sixteen patients with increased elastic recoil had a greater increase in the distance walked in six minutes than the other four patients, in whom recoil did not increase (P=0.02). The improved lung recoil led to disproportionate decreases in residual volume as compared with total lung capacity (16 percent vs. 6 percent), but the decreases in both values were significant (P<0.001). Forced expiratory volume in one second increased (from 0.87+/-0.36 to 1.11+/-0.45 liters, P<0.001). End-expiratory esophageal pressure also decreased (P=0.002). These improvements in lung mechanics led to a decrease in arterial partial pressure of carbon dioxide form 42+/-6 to 38+/-5 mm Hg (P=0.006). Furthermore, the fractional change in right ventricular area, an indicator of systolic function, increased from 0.33+/-0.11 to 0.38+/-0.010 (P=0.02). CONCLUSIONS: Lung-reduction surgery can produce increases in the elastic recoil of the lung in patients with diffuse emphysema, leading to short-term improvement in dyspnea and exercise tolerance.

Lung reduction surgery for emphysema.

Lung reduction surgery, a procedure that entails removal of portions of the most diseased lung tissue in patients with diffuse emphysema, has been resurrected based on advances in surgical technique, radiographic imaging, and pulmonary physiologic assessment. We outline potential mechanisms for improvement in pulmonary mechanics, gas exchange, pulmonary vascular function, and exercise tolerance following surgery. Available literature is reviewed, and patterns that are beginning to emerge with respect to optimal surgical approach and patient selection criteria are presented. Early results suggest that this procedure offers real hope to our patients; however, long-term follow-up studies will be necessary to define its ultimate utility.

Unilateral thoracoscopic surgical approach for diffuse emphysema.

We evaluated the use of a lateral thoracoscopic approach for lung reduction surgery in patients with diffuse emphysema. Sixty-seven patients with a mean age of 61.9 years underwent operation. Operative side was determined by preoperative imaging. The procedures were laser ablation in 10 patients and stapler resection in 57 patients. Ten patients, including six of the 10 patients in the laser-only group had poor outcome (death or hospitalization longer than 30 days), leading us to abandon the laser technique. Of the remaining 57 patients undergoing primary stapled resection, duration of chest tube placement averaged 13 days (range 3 to 53 days) with a mean hospital stay of 17 days (range 6 to 99 days). Seven patients required ventilation for longer than 72 hours, six patients underwent conversion of the procedure to open thoracotomy, four patients acquired arrhythmias, and three patients were treated for empyema. There was one early death (1.7%), from cardiopulmonary failure. Forty patients returned for 3-month evaluation. Significant (p < 0.0001) improvements were seen in forced vital capacity (2.69 L after vs 2.26 L before) and forced expiration volume in 1 second (1.04 L after vs 0.82 L before), with 25 of 40 patients (63%) showing an improvement of more than 20%. Lung volume measures, in particular residual volume, fell significantly. Arterial blood gas analysis revealed that carbon dioxide tension fell significantly in patients with preoperative hypercapnia (carbon dioxide tension > 45 mm Hg, p = 0.018). Six-minute walk test results improved (894 feet after vs 784 feet before, p = 0.002), and symptomatic benefit was confirmed by significant improvement in the dyspnea index. The combination of both hypercapnia and reduced single-breath diffusing capacity for carbon monoxide was significantly more frequent (p = 0.0026) and was 86% specific (5 of 6 patients) in predicting serious postoperative risk. We conclude that the lateral thoracoscopic surgical approach to diffuse emphysema offers significant improvement in pulmonary mechanics and functional impairment. Patients with a combination of hypercapnia and reduced single-breath diffusing capacity for carbon monoxide should not be considered for this procedure because of significant perioperative risk.