Underestimation of mortality following lung volume reduction surgery resulting from incomplete follow-up.

STUDY OBJECTIVES: Incomplete follow-up can bias interpretation of data that are collected in longitudinal studies. We noted that many patients failed to return for follow-up in a study of effect of lung volume reduction surgery (LVRS) on quality of life (QOL). Accordingly, we designed this investigation to determine the reasons patients dropped out, and to assess differences between those who continued in the study (attendees) and those who did not (nonattendees). DESIGN: Telephone survey. SUBJECTS: Patients with advanced emphysema who had undergone LVRS and had previously agreed to participate in a longitudinal QOL study. RESULTS: No differences were found with regard to age, gender, preoperative pulmonary function, or oxygen use between attendees and nonattendees. Long-term mortality in nonattendees (27%) was considerably greater than that seen in attendees (3%, p < 0.05). Distance from the hospital, financial burden, and living out of the region were the most common reasons cited by surviving nonattendees for their failure to return for follow-up. CONCLUSIONS: Studies reporting the long-term mortality after LVRS can be biased in the direction of underestimating the true value if they are compromised by incomplete follow-up.

Prone ventilation.

Considerable clinical experience confirms that oxygenation can be improved in many patients with ARDS by employing prone ventilation. The improvement occurs because, in the prone position, the lung fits into the thorax such that lung distention is more uniform and compressive forces extant in the supine position, which serve to cause dorsal airspace collapse, are reduced. Whether these changes translate into improved clinical outcomes has yet to be determined, but prone ventilation has the potential of reducing oxygen toxicity and limiting ventilator-induced lung injury.

The prone position eliminates compression of the lungs by the heart.

The prone position improves gas exchange in many patients with ARDS. Animal studies have indicated that turning prone restores ventilation to dorsal lung regions without markedly compromising ventral regions. To investigate a potential mechanism by which this might occur, the relative volume of lung located directly under the heart was measured in the supine and prone positions in seven patients. Four axial tomographic sections between the carina and the diaphragm were analyzed (Sections 1 through 4). When supine, the percent of the total lung volume located under the heart increased from 7 +/- 4% to 42 +/- 8%, and from 11 +/- 4% to 16 +/- 4% in Sections 1 through 4, in the left and right lungs, respectively. When prone, the percent of left and right lung volume located under the heart was

Effect of zonal conditions and posture on pulmonary blood flow distribution to subpleural and interior lung.

Observations made on vessels seen directly beneath the pleura may not accurately reflect what occurs in vessels located deeper in the interior of the lung. We quantified flow to subpleural and deeper, interior regions under zone 1 or 2 conditions in excised (n = 5) and in vivo (n = 6) rabbit lungs, in the head-up or inverted position. After infusion of radiolabeled microspheres, lungs were dried at alveolar pressure of 25 cmH(2)O and sliced in 1-cm sections along the gravitational plane and in three planes in the dorsal-ventral axis. Regions located <1 mm from the pleural surface were dissected away from the remaining tissue. In both zonal conditions, 1) weight-normalized flow to the interior exceeded that found in subpleural regions; and 2) flow followed the gravitational gradient, with the correlation varying with the scale of measurement. We conclude that flow through subpleural vessels is less than that which occurs deeper in the interior, but the regional distributions of flow and the effects of zonal conditions are similar in the two regions.

Lung volume reduction surgery has variable effects on blood gases in patients with emphysema.

Most studies of bilateral lung volume reduction surgery (LVRS) report increases in arterial oxygenation (PaO2). Some suggest this results from an increased alveolar ventilation, but others imply that ventilation-perfusion heterogeneity is reduced. We measured arterial blood gases (ABGs) on air before and 3 mo following LVRS in 46 patients (61% of eligible patients), estimate the difference between alveolar and arterial O2 (AaPO2), and correlated the changes observed with preoperative ABGs, and with pre-and postoperative pulmonary function. The mean +/- SD change in PaO2 and AaPO2 was +3 +/- 10 mm Hg (p = 0.058) and +1 +/- 11 mm Hg (p = NS), respectively, and the range of change was large (-17 to +29 mm Hg and -24 to +23 mm Hg, respectively). The mean change in PaCO2 was -3 +/- 5 mm Hg (p < 0.05) and ranged from -11 to +5 mm Hg. Changes in PaO2 and AaPO2 were poorly correlated with changes in PaCO2 or with pre- or postoperative pulmonary function. Although some patients had a marked improvement in ABGs following LVRS, almost as many deteriorated. On average, only minimal effects were seen. Although mean alveolar ventilation improved somewhat, the effect of LVRS on PaO2 primarily resulted from alterations in ventilation-perfusion heterogeneity.

Dyspnea resulting from fibromyalgia.

Two patients with chronic, severe, episodic dyspnea underwent prolonged, extensive, and invasive evaluations without a diagnosis being made. Both were subsequently diagnosed with fibromyalgia, and therapy directed at this condition resulted in resolution of their symptoms. Fibromyalgia is rarely included in the differential diagnosis of dyspnea, and timely diagnosis and treatment may be delayed. However, this condition must be considered because it can only be established by seeking the appropriate history and physical findings.

Lung-volume reduction surgery for diffuse emphysema: radiologic assessment of changes in thoracic dimensions.

Patients with severe, diffuse emphysema may be candidates for pneumectomy (lung-volume reduction surgery, LVRS) to improve lung and respiratory muscle function. To identify candidates who might benefit from this surgery, it is necessary to understand how lung volumes and respiratory function are effected. In this article, the authors demonstrate a significant difference in lung size on chest radiographs obtained before and after surgery. Thirty-five of 71 consecutive patients undergoing LVRS had both preoperative and postoperative chest radiographs and pulmonary function tests available for retrospective review. Preoperative and postoperative measurements of lung height, transthoracic diameters, mediastinal width, heart size, diaphragmatic arc, and intercostal spaces were compared using paired t-tests. Radiographic measurements where also correlated with changes in lung volumes as measured by pulmonary function tests. Lung heights (right, left, mean lateral) and coronal diameter at the aortic arch were reduced after surgery (all p < 0.05). Forced vital capacity, forced expiratory volume in 1 second (FEV1), and vital capacity increased, and total lung capacity and residual volume decreased after surgery (all p < 0.05). Left lung height showed a significant correlation (p = 0.025) with FEV1; all other correlations between radiographic changes and pulmonary function test changes were not significant. The explanation for improved lung function in patients after LVRS is not completely clear and is probably multifactorial. Radiologic alterations reflect anatomic changes caused by surgery and support the theory that modifications of chest wall configuration occur and are likely responsible, in part, for improved symptomatology and respiratory function.

Estimated growth of lung volume reduction surgery among Medicare enrollees: 1994 to 1996.

OBJECTIVE: To estimate the number of lung volume reduction surgery procedures performed on Medicare enrollees from 1994 to 1996. DESIGN: Statistical analysis of national Medicare claims data. PATIENTS: All Medicare enrollees with emphysema hating claims records for pulmonary resection procedures from January 1, 1993, through December 31, 1996. MAIN OUTCOME MEASURE: Estimated number of lung volume reduction procedures performed per month from July 1994 through December 1996. RESULTS: An estimated 1,212 lung volume reduction procedures were performed on Medicare enrollees between July 1994 and December 1995 (95% confidence interval, 1,012 to 1,408). Nearly one half of these procedures were performed in the last 3 months of 1995. At the time Health Care Financing Administration announced that it would suspend reimbursement for the procedure (December 1995), lung volume reduction surgery was being performed in 37 states. The number of claims per month decreased from a peak of 169 in December 1995, to 11 in March 1996. Average Medicare reimbursement per procedure was $31,398. CONCLUSIONS: Lung volume reduction surgery for patients increased rapidly following its reintroduction in 1994. The growth of lung volume reduction surgery demonstrates that widespread adoption and utilization of a surgical procedure can occur in the absence of data from controlled clinical trials. Medicare expenditures for lung volume reduction surgery were an estimated $30 million to $50 million. Performing the surgery for all current Medicare patients who meet the appropriate clinical criteria would cost an estimated $1 billion.

Surgical options for patients with advanced emphysema.

Since the early 1900s, a variety of operations have been suggested for emphysema but, with the exception of giant bullectomy, an option in only a small fraction of patients, none has proven effective. Data collected by a number of academic medical centers indicate that LVRS may ameliorate symptoms and improve pulmonary physiology, function, and quality of life in appropriately selected patients with emphysema. Accordingly, LVRS may provide an opportunity to intervene in a rapid, effective, and, possibly, cost-effective manner in a debilitating, chronic disease. That is an extraordinarily attractive proposition for both patients and physicians alike. But a number of questions remain: (1) What is the effect of LVRS compared with maximal medical therapy? (2) What is the duration of any beneficial effect of LVRS? (3) What is the best operative approach? (4) What patient characteristics predict good and bad outcomes? (5) What is the role of pre- and, possibly, postoperative pulmonary rehabilitation? (6) Does LVRS adversely affect the rate of loss of lung function over time, as some have suggested? (7) What is the cost of LVRS compared with standard medical therapy? (8) Can the procedure be performed safely in nontransplant centers? (9) What is the effect on disease-specific quality of life? (10) Does it affect mortality? A prospective, randomized controlled trial involving 18 selected centers will begin in the fall of 1997 under the sponsorship of the Health Care Financing Corporation (the administrators of Medicare) and the National Institutes of Health. We strongly support the creative, collaborative approach that has been taken by those two government agencies to stimulate this study. The need for controlled trials of new therapies cannot be overstated; only with such trials can the questions enumerated above be answered with certainty.

Lung volume reduction surgery improves maximal O2 consumption, maximal minute ventilation, O2 pulse, and dead space-to-tidal volume ratio during leg cycle ergometry.

Early experience suggests that lung volume reduction surgery improves exercise tolerance as measured by the 6-min walk distance in patients with emphysema. To identify the physiologic mechanism(s) by which lung volume reduction surgery improved exercise, we performed progressive cardiopulmonary exercise testing, including rest and peak exercise blood gas determinations, on 21 consecutive patients before and 3 mo after lung volume reduction surgery. Maximal work (median, range, % change) increased 17.5 watts (-13 to +44 watts, 46%, p < 0.05), maximal oxygen consumption increased 0.16 L/min (-0.17 to +0.48, 25%, p < 0.05), maximal ventilation increased 6.6 L/min (-7 to +26 L/min, 27%, p < 0.05), and the dead space/tidal volume ratio at peak exercise decreased 0.07 (-0.22 to +0.09, 12%, p < 0.05), exclusively as a result of an increase in the tidal volume. After lung volume reduction surgery heart rate decreased at the point of isowatt exercise, from 115 to 111 beats/min (p < 0.05). No difference was observed in the other physiologic variables measured at isowatt exercise. In 13 patients exercised while breathing room air, the alveolar-to-arterial O2 difference increased, and the arterial O2 tension decreased from rest to peak exercise both before and after the operation, but significant changes in this response were not observed after surgery. The primary problem limiting exercise performance in these patients was the limited ventilatory capacity as 16 and 13 of the 21 subjects developed acute respiratory acidemia at peak exercise before and after surgery, respectively. Lung volume reduction surgery in patients with severe emphysema improved maximal ventilation, thereby improving maximal exercise performance.

Influence of the route of allergen administration and genetic background on the murine allergic pulmonary response.

We used various ovalbumin sensitization and challenge protocols to determine the importance of the route of allergen administration and the genetic background in modulating the physiologic, inflammatory, and immunologic features characteristic of allergen-induced asthma. In BALB/c mice, induction of maximal airway hyperresponsiveness and airspace eosinophilia required administration of ovalbumin by both the intraperitoneal and the intranasal routes (combination protocol), whereas intraperitoneal immunization alone resulted in maximal ovalbumin-specific IgE plasma levels. Thus, a systemic immune response to allergen, in addition to, or independent of IgE production, as well as local allergen challenge were necessary for maximal induction of pulmonary disease. BALB/c mice treated with ovalbumin by the combination protocol had increased Th2-type cytokine mRNA levels in bronchial lymph node tissue compared with control mice. In contrast, C57BL/6 mice treated with ovalbumin by the combination protocol had significantly decreased responses compared with BALB/c mice for all parameters of allergic pulmonary disease examined, with the exception of airspace eosinophilia. Genetic background has a striking and selective effect on the phenotype of murine allergic pulmonary disease. Further analysis of this murine model should be useful in helping define the critical pathogenetic events in allergen-induced asthma.