Histologically confirmed tuberculosis-associated obstructive pulmonary disease.

Although chronic airflow limitation (CAL) is an important long-term consequence of tuberculosis (TB), little is known about the disease process. We present what we believe to be the first case of histologically confirmed residual TB-associated obstructive pulmonary disease (TOPD) in a 23-year-old non-smoking man who developed severe CAL after one episode of TB, with no other plausible risk factors. Lung biopsies identified residual post-TB pathology affecting the small airways and vessels throughout his lung; this has not been reported previously. These findings strengthen the argument that TOPD may be a phenotype of CAL distinct from both smoking-related chronic obstructive pulmonary disease and bronchiectasis.

Calcium-induced release of 5-hydroxytryptamine from thyroid lobes in vitro and accompanying ultrastructural changes in parafollicular and follicular cells.

Biogenic amines, including serotonin (5-HT), have been shown to activate follicular cells of the thyroid. 5-HT is stored in bat's parafollicular cells. Previous radioautographical evidence indicates that this 5-HT is present in calcitonin granules. The present study was done to determine if Ca++, the natural stimulus to calcitonin release, would also release parafollicular cell 5-HT and, if so, whether this release would be accompanied by activation of follicular cells. Parafollicular cells were filled with labeled 5-HT by incubation of thyroid lobes of bats or mice with 5-[3H]hydroxytryptophan, the precursor of [3H]5-HT. Thyroid lobes were incubated in vitro in Ca++-free medium containing a chelating agent and were then challenged with Ca++ (0-30 mM). Release of [3H]5-HT was defected beginning at 5 mM Ca++. [3H]5-HT release was roughly proportional to the Ca++ concentration. Calcium challenge also affected thyroid ultrastructure in bats. After 10-min exposure to 30 mM Ca++, there were an increased number and centripetal movement of follicular cell lysosomes, development of apical pseudopods, and formation of colloid droplets. Many lysosomes also developed a crystalline-like matrix. An unique membrane-enclosed, rod-shaped organelle appeared in a small number of follicular cells. Parafollicular cells exposed to high concentrations of Ca++ were often degranulated, although many appeared unchanged. These changes confirm that 5-HT is released from parafollicular cells by elevating the external Ca++ concentration, supporting the hypothesis that 5-HT and calcitonin share storage granules. 5-HT release may mediate the activation of follicular cells by Ca++.

Multiple peripheral pulmonary carcinoids and tumorlets of carcinoid type, with restrictive and obstructive lung disease.

Multiple peripheral carcinoid tumors were found on lung biopsy in a 53 year old woman with an eight year history of pulmonary nodules. The biopsy specimen showed nodules varying from 1 to 7 mm in greatest diameter. The larger lesions were typical bronchial carcinoids whereas the smaller ones resembled pulmonary "tumorlets." Electron microscopy showed neurosecretory granules typical of carcinoids. The common multicentric origin of carcinoids and tumorlets from Kulchitsky cells is discussed. Pulmonary function testing revealed mild obstructive and restrictive defects, both attributed to the carcinoid tumors. The history, pathology and physiology of this unusual case are presented in detail, with a review of the literature. Obstructive airways disease, presumably due to the extensive bronchiolar involvement, has not previously been reported in this entity.

Effect of postoperative radiotherapy on changes in pulmonary function in patients with stage II and IIIA lung carcinoma.

To assess the pulmonary tolerance to postoperative radiotherapy (RT) in patients with resected lung carcinoma, a prospective study was begun in January 1977, which consisted of (a) initial pulmonary function test (PFT) and arterial blood gases (ABG) at 1 month after surgery, and before beginning of postoperative RT, and (b) follow-up PFT and ABG 1 year after postoperative RT and then every year thereafter. As of December 1987, 137 patients have been enrolled into this study, and 71 patients who were free of recurrence were subjected to the follow-up PFT and ABG. The remaining 66 patients were unable to complete the follow-up studies because of recurrent carcinoma in 60, refusal to participate in the study in 5 patients even in the absence of significant respiratory symptoms, and progressive asbestos-related pleural thickening in 1 patient. The patient characteristics were as follows: Age ranged from 27 to 79 years with the median of 59 years; sex ratio was 1.4 to 1 for male to female; surgical procedures included lobectomy in 49 and pneumonectomy in 22 patients; tumor extent consisted of Stages T1-T2N1M0 in 44, T1-T2N2M0 in 9, and T3N0-N2M0 in 18 patients, respectively. Histologic types included squamous cell carcinoma in 26, adenocarcinoma in 42, small cell carcinoma in 1, and large cell carcinoma in 2 patients. Target volume for RT included the ipsilateral hilum, the mediastinum, and the thoracic inlet including both supraclavicular fossae. A total dose of 54 Gy was delivered in 1.8 Gy of daily fractions, 5 days per week over a period of 6 weeks. Contrary to expectation, there were minor changes in PFT indices in both lobectomy and pneumonectomy patients. The follow-up PFT in the lobectomy group showed small -3% to +2% changes in mean values of ventilatory indices, lung volume, and ABG. The follow-up PFT in the pneumonectomy group also showed small -9% to +13% changes in mean values of ventilatory indices, lung volume, and ABG. Sixteen patients have had more than one PFT during the follow-up period (2 years to 10 years), and there was no significant long term adverse effect of RT on PFT in this subset of patients. Lung scans assessing regional function, which were available in six patients, were not helpful in predicting changes in PFT indices as a result of postoperative RT.

Evaluation of bepridil for the treatment of angina pectoris: evidence for preservation of left ventricular function.

The efficacy of bepridil (400 mg once a day) was assessed in 15 patients with exertional angina pectoris. All 15 patients reported substantial clinical improvement during bepridil treatment compared with placebo treatment. Episodes of angina were 11.8 +/- 4.1 (mean +/- standard error of the mean)/week with placebo and 3.8 +/- 1.6 with bepridil (p less than 0.05); nitroglycerin use was 9.1 +/- 3.3 tablets/week with placebo and 3.5 +/- 1.7 with bepridil (p less than 0.05). Five of 15 patients receiving bepridil did not experience angina during treadmill exercise; in the remaining 10 patients, time to onset of angina during exercise was 5.7 +/- 0.9 minutes with bepridil as opposed to 4.5 +/- 0.8 minutes with placebo (p less than 0.05). Left ventricular (LV) performance at peak exercise as measured by first-pass radionuclide angiography revealed the ejection fraction to be 38 +/- 3% during placebo therapy and 47 +/- 4% during bepridil therapy (p less than 0.0025). End-diastolic LV volume was unchanged, but end-systolic volume was 136 +/- 11 and 117 +/- 13 ml (p less than 0.05) and stroke volume was 82 +/- 6 and 97 +/- 9 ml (p less than 0.05) during placebo and bepridil therapy, respectively. Heart rate at peak exercise was 136 +/- 3 beats/min with placebo and 128 +/- 3 beats/min with bepridil; however, blood pressure was unchanged. These studies demonstrate that bepridil results in significant clinical improvement and enhanced LV performance in patients with angina pectoris.

Left ventricular ejection fraction response during exercise in asymptomatic systemic hypertension.

To study the effect of mild-to-moderate elevations in diastolic blood pressure (BP) on systolic left ventricular (LV) function, 28 hypertensive patients and 20 normal subjects underwent upright exercise first-pass radionuclide angiography. All were asymptomatic, had normal rest and exercise electrocardiographic findings and no evidence of LV hypertrophy or coronary artery disease. LV function at rest was similar in the 2 groups, but with exercise hypertensive patients had a greater end-systolic volume (69 +/- 19 vs 51 +/- 19 ml, p less than 0.002) and lower ejection fraction (EF) (0.59 +/- 0.09 vs 0.72 +/- 0.07, p less than 0.0001), stroke volume (101 +/- 28 vs 130 +/- 36 ml, p less than 0.005) and peak oxygen uptake (23 +/- 7 vs 33 +/- 9 ml/kl/min, p less than 0.05). Hypertensive patients were separated into 3 groups: group 1-12 patients with an increase in EF with exercise greater than or equal to 0.05; group 2-7 patients with a change in EF with exercise less than 0.05; and group 3-9 patients with a decrease in EF with exercise greater than or equal to 0.05. Group 3 hypertensive patients were older, had a higher heart rate at rest and lower peak oxygen uptake. Rest LV function was similar in the 3 hypertensive subgroups, but exercise end-systolic volumes were higher in groups 2 and 3. Exercise thallium-201 images was normal in all but 1 of 14 hypertensive group 2 or 3 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Prediction of postoperative pulmonary function following thoracic operations. Value of ventilation-perfusion scanning.

Surgical resection of lung cancer is frequently required in patients with severely impaired lung function resulting from chronic obstructive pulmonary disease. Twenty patients with obstructive lung disease and cancer (mean preoperative forced expiratory volume in 1 second [FEV1] = 1.73 L) were studied preoperatively and postoperatively by spirometry and radionuclide perfusion, single-breath ventilation, and washout techniques to test the ability of these methods to predict preoperatively the partial loss of lung function by the resection. Postoperative FEV1 and forced vital capacity (FVC) were accurately predicted by the formula: postoperative FEV1 (or FVC) = preoperative FEV1 X percent function of regions of lung not to be resected (r = 0.88 and 0.95, respectively). Ventilation and perfusion scans are equally effective in prediction. Washout data add to the sophistication of the method by permitting the qualitative evaluation of ventilation during tidal breathing. Criteria for patients requiring the study are suggested.

Pulmonary cholesterol crystal embolization.

BACKGROUND: Cholesterol crystal embolization (CCE) has been documented to affect nearly every organ system. However, CCE involving the lung is distinctly uncommon and has been documented only in the setting of an aortocaval fistula. DESIGN: A case at the Massachusetts General Hospital and a MEDLINE search of English-language medical articles published between 1966 and 1997 provide the basis for this report. RESULTS: The precipitants of CCE include invasive vascular procedures, anticoagulant therapy, and thrombolysis. The most common symptoms include claudication of the calf, gastrointestinal bleeding, and weight loss. The most common signs include livedo reticularis, gangrene, and ulcers. Azotemia, proteinuria, normocytic anemia, and eosinophilia often are found. Herein is described the first pathologically confirmed case of CCE to the lung in the absence of an arteriovenous fistula. CONCLUSION: Pulmonary hemorrhage should now be included in the diverse list of presenting signs of CCE. Moreover, CCE should be considered in the differential diagnosis of pulmonary-renal syndromes.

Ammonium ion and the anaerobic threshold in man.

To determine if ammonium ion plays a role in the lactate and ventilatory thresholds of incremental exercise, we investigated the effects on blood lactate and ventilation of NH(4+)-buffering by monosodium glutamate. Six normal volunteers underwent intravenous loading with MSG, 9 g, in a randomized, double-blind, saline placebo controlled crossover study. Four of the six subjects had a greater than 10 percent fall in peak (NH4+) following MSG (37 +/- 2.0 vs 25 +/- 4.3 micrograms/dl p = 0.003, PLB vs MSG). When MSG blunted the rise in venous (NH4+) during exercise, uncoupling of the LT and VT was observed. Specifically, with suppression of peak exercise (NH4+) by MSG, the LT was delayed (r = -0.84, p = 0.03), the VT was earlier (r = 0.86, p = 0.02), and the VO2 difference between the LT and VT widened (r = -0.90, p = 0.02). We conclude that NH4+ plays a role in determining the LT and VT of incremental exercise and that the VT may not be exclusively dependent on blood lactate.

Breathing reserve at the lactate threshold to differentiate a pulmonary mechanical from cardiovascular limit to exercise.

STUDY OBJECTIVES: Criteria used to define the respective roles of pulmonary mechanics and cardiovascular disease in limiting exercise performance are usually obtained at peak exercise, but are dependent on maximal patient effort. To differentiate heart from lung disease during a less effort-dependent domain of exercise, the predictive value of the breathing reserve index (BRI=minute ventilation [VE]/maximal voluntary ventilation [MVV]) at the lactate threshold (LT) was evaluated. DESIGN: Thirty-two patients with COPD and a pulmonary mechanical limit (PML) to exercise defined by classic criteria at maximum oxygen uptake (VO2max) were compared with 29 patients with a cardiovascular limit (CVL) and 12 normal control subjects. Expired gases and VE were measured breath by breath using a commercially available metabolic cart (Model 2001; MedGraphics Corp; St. Paul, Minn). Arterial blood gases, pH, and lactate were sampled each minute during exercise, and cardiac output (Q) was measured by first-pass radionuclide ventriculography (System 77; Baird Corp; Bedford, Mass) at rest and peak exercise. RESULTS: For all patients, the BRI at lactate threshold (BRILT) correlated with the BRI at VO2max (BRIMAX) (r=0.85, p<0.0001). The BRILT was higher for PML (0.73+/-0.03, mean+/-SEM) vs CVL (0.27+/-0.02, p<0.0001), and vs control subjects (0.24+/-0.03, p<0.0001). A BRILT > or = 0.42 predicted a PML at maximum exercise, with a sensitivity of 96.9%, a specificity of 95.1%, a positive predictive value of 93.9%, and a negative predictive value of 97.5%. CONCLUSIONS: The BRILT, a variable measured during the submaximal realm of exercise, can distinguish a PML from CVL.

Cannulation of the proximal aorta during long-term membrane lung perfusion.

Prolonged extracorporeal oxygenator support for acute respiratory failure is a clinical reality. Recent experience with 4 patients has demonstrated an advantage in delivery of saturated blood to the root of the aorta during venoarterial (VA) bypass. We have been able to perfuse the heart and bilateral cerebral hemispheres by advancing the tip of a large perfusion cannula to the aortic root from the common femoral artery. When the catheter did not pass beyond the transverse aortic arch, there was marked asymmetry of oxygenator perfusion, as determined by differential oxygen tension in right and left radial artery blood and by xenon-133 scans following isotope injection into the arterial return line. Long-term VA bypass lasting from 5 to 11 days resulted in long-term survival in 2 patients with post-traumatic gram-negative pneumonitis. The other patients, who had viral pneumonitis and post-transfusion respiratory failure, died after 9 and 11 days of membrane oxygenator support. No embolic lesions or arterial or valvular injuries were discovered at autopsy. This is a safe and useful method of providing oxygenated blood to the aortic root for equal distribution to the rest of the body.

Left ventricular function before and after reaching the anaerobic threshold.

Simultaneous pulmonary gas exchange analysis and exercise radionuclide angiography were performed in 24 normal patients (14 supine and ten upright). Left ventricular (LV) volumes and ejection fraction (EF) were measured at rest, anaerobic threshold (point of nonlinear increase in ventilation relative to oxygen uptake), and peak exercise. The anaerobic threshold occurred at a similar heart rate for supine vs upright exercise, 78 percent and 77 percent of peak heart rate, respectively. The anaerobic threshold occurred at a similar workload for supine vs upright exercise, 60 percent and 56 percent of peak workload, respectively. The anaerobic threshold also occurred at a similar oxygen uptake for supine vs upright exercise, 69 percent vs 69 percent of peak oxygen uptake, respectively. For both exercise modes, mean LVEF increased (p less than 0.01) by a similar amount (.06 vs .07) from rest to anaerobic threshold, but there was no further increase from anaerobic threshold to peak exercise. The mechanism of the increase was a reduction in end-systolic volume with little or no change in end-diastolic volume. This increase was not seen in patients with rest LVEF in the high normal range (greater than 0.68). Therefore, for both supine and upright exercise, the major augmentation in LVEF occurs at earlier stages of exercise, prior to the anaerobic threshold. After the anaerobic threshold, the LVEF response may be highly variable, and a uniform increase is not necessarily expected even in normal subjects.

Embolization of pulmonary catheter-induced pulmonary artery pseudoaneurysms.

STUDY OBJECTIVES: To determine the outcome of patients with pulmonary catheter-induced pulmonary artery pseudoansurysms (PSAs) treated with embolization. DESIGN: Retrospective outcomes review. SETTING: Large urban tertiary-care hospital. PATIENTS: All patients who presented to diagnostic angiography for ruptured pulmonary artery PSA caused by pulmonary artery catheters (PACs) from November 1990 to September 1995. A total of six patients were examined. INTERVENTIONS: Transcatheter embolotherapy with coils, absorbable gelatin sponges (Gelfoam), and suture material. RESULTS: These procedures were technically successful in all patients, and none had recurrent hemoptysis. Four of the six patients were discharged from the hospital. CONCLUSION: Embolotherapy is a useful alternative to surgery for some patients with PAC-induced pulmonary PSA.

Preoperative predictors of operative morbidity and mortality in COPD patients undergoing bilateral lung volume reduction surgery.

Bilateral volume reduction surgery (VRS) improves lung function for selected patients with emphysema. However, predictors of outcome are not well defined. We reviewed the preoperative characteristics of the first 47 consecutive patients who underwent bilateral VRS at the Massachusetts General Hospital in order to define potential predictors of unacceptable outcome. Preoperative data included spirometry, plethysmography, diffusion of carbon monoxide (Dco), maximum inspiratory pressure (MIP), maximum expiratory pressure, resting arterial blood gases (ABG), cardiopulmonary exercise testing with ABG and lactate sampling, and radionuclide ventriculography. Prepulmonary and postpulmonary rehabilitation 6-min walk tets (6MWT), and preoperative chest CT scans were also obtained. Twenty-two subjects were male and 17 of the subjects were on the lung transplant list. Patient characteristics included age of 60.5 +/- 7.5 years, FEV1 of 0.67 +/- 0.20 L, total lung capacity of 7.56 +/- 1.7 L, Dco of 7.40 +/- 4.1 mL/min/mm Hg, and PaCO2 of 41.6 +/- 6.4 mm Hg (mean +/- SD). The FEV1, vital capacity, MIP, resting room air PaCO2, prepulmonary and postpulmonary rehabilitation 6MWT, and PaCO2 at maximum oxygen consumption correlated with length of hospitalization (p < 0.05). Based on analysis of 41 of 47 patients for whom there were complete data, the inability to walk more than 200 m on the 6MWT before or after preoperative pulmonary rehabilitation, and resting PaCO2 > or = 45 mm Hg were the best predictors of an unacceptable outcome. If either of these characteristics was present, six of 16 vs zero of 25 died (Fisher's Exact Test, p = 0.0025, one-tailed) and 11 of 16 vs four of 25 had hospital courses > 21 days (p < 0.002). Both the 6MWT < 200 m and resting PaCO2 > or = 45 mm Hg alone correlated with death (p = 0.004 and p = 0.012, respectively) and the resting PaCO2 > or = 45 mm Hg correlated with hospital days > 21 (p = 0.0002). In conclusion, the data suggest that the inability to walk at least 200 m in 6 min before or after pulmonary rehabilitation and a resting room air PaCO2 > or = 45 mm Hg are excellent preoperative predictors of unacceptable postoperative outcomes.

Toxicity of thoracic radiotherapy on pulmonary function in lung cancer.

Physiological changes in pulmonary function (PF) as a result of radiation therapy (RT) or radiation therapy plus chemotherapy (RT + CT) for unresectable lung cancer were evaluated in an ongoing prospective study and an attempt was also made to define a guideline which can be used to minimize adverse effect of RT on pulmonary function before RT is given. The study design consisted of: (a) standard overall pulmonary function test (PFT); (b) regional PFT, i.e. a quantitative analysis of regional distribution of ventilation, perfusion and volume using 13N and a positron camera before RT; and (c) follow-up studies of standard PFT every 6 months for 3 years after RT or RT + CT. Predicted post-RT PF prior to RT was calculated by a formula: predicted FEV1 after RT = FEV1 before RT x (1 - an average of the percent of ventilation and perfusion contributed by lung tissue within the RT treatment volume). A total of 267 patients with unresectable, but still potentially curable lung cancer by RT were entered into this study, and 135 patients who were free of recurrence underwent repeat studies. Loss of PF as a result of RT is closely related to the degree of PF reserve prior to RT. Patients with FEV1 > 50% of the predicted showed a statistically significant decrease in FEV1, FVC, MBC, peak expiratory flow rate and DLCO, i.e. a 22% loss of the initial value. Airway resistance was increased by 31%. Two-thirds of this group of patients showed a decrease in PF as predicted by the above formula. For patients with limited PF reserve defined by FEV1 < 50% of the predicted, the pattern of PF loss after RT was quite different. An improvement in PF although it was < or = 10%, contrary to the prediction, was noted in 50% of patients, and another 37% of patients showed a small decrease in PF (< or = 10% of the initial value). Only 13% of patients showed a loss of pulmonary function as predicted by regional PF data. Patients with a significant shift (> 10%) of ventilation and/or perfusion to the uninvolved side of the lung by centrally located primary tumor or involved lymph nodes showed an increase in PF in 60% of patients after RT, and another 20% of patients showed a minor decrease in PF (< 10% of the initial value). Only 20% of these patients showed a decrease in pulmonary function as predicted by regional PF data. Guidelines for minimizing adverse effect of RT on PF, which are based on the initial PF reserve and regional PF data, are presented.

31P nuclear magnetic resonance spectroscopy study of the anaerobic threshold in humans.

The relationships among the lactate threshold (LT), ventilatory threshold (VT), and intracellular biochemical events in exercising muscle have not been well defined. Therefore 14 normal subjects performed incremental plantar flexion to exhaustion on 2 study days, the first for determination of LT and VT and the second for continuous 31P nuclear magnetic resonance spectroscopy of calf muscle. Exercising calf muscle pH fell precipitously at 66.4 +/- 3.4% (SE) of the maximum O2 uptake (VO2max) and was termed the intramuscular pH threshold. This did not occur at a significantly different metabolic rate from that at the LT (78.6 +/- 5.9% VO2max) or at the VT (75.0 +/- 4.1% VO2max, P = 0.15 by analysis of variance). Four subjects showed an intramuscular pH threshold and VT without a perceptible rise in forearm venous blood lactate. It is concluded that traditional markers of the "anaerobic threshold," the LT and VT, occur as intramuscular pH becomes acid for a group of normal subjects undergoing incremental exercise to exhaustion. It is speculated that neuronal pathways linking intramuscular biochemical events to the ventilatory control center may explain the intact VT in those subjects without an "intermediary" LT.

Postpneumonectomy syndrome: diagnosis, management, and results.

Airway obstruction may be caused by extreme mediastinal shift and rotation after right pneumonectomy or after left pneumonectomy in the presence of a right aortic arch. Eleven adults (aged 18 to 58 years) with severe symptoms were treated surgically between 5 months to 17 years after pneumonectomy (7 right, 4 left). An initial patient with only one functional lobe was treated unsuccessfully by aortic division and bypass graft. Ten underwent mediastinal repositioning. After two recurrences prostheses were used to maintain mediastinal position. Five patients who underwent such repositioning are doing well from 5 months to more than 5 years later. One died 1 month after operation probably of pulmonary embolism. One who showed residual airway collapse after operation has some recurrent obstruction. Three other patients who showed severe malacic obstruction of the airway after mediastinal repositioning variously underwent aortic division with bypass graft and tracheal and bronchial resection. One is well almost 6 years later. Two died postoperatively. Occurrence of the syndrome is unpredictable. Where malacic changes have not occurred, mediastinal repositioning may reasonably be expected to correct obstruction. Optimal treatment for concurrent severely malacic airways is unclear.

The response of cardiac and pulmonary disease to exercise testing.

The features of cardiovascular and pulmonary disease in exercise testing are described. In general, ventilatory limitation is the most common factor in lung disease. An early anaerobic threshold and a decreased VO2 mix in the absence of ventilatory limitation is the usual feature of severe heart disease.