K. Scott Miller

Evaluation and management of scleroderma lung disease using bronchoalveolar lavage

PURPOSEnBronchoalveolar lavage (BAL) was performed in 43 nonsmoking patients with scleroderma (systemic sclerosis) to determine the frequency of alveolitis, the status of BAL findings over time, and the relationship of such findings to pulmonary status initially and at follow-up.nnnPATIENTS AND METHODSnForty-three nonsmoking patients with systemic sclerosis underwent extensive pulmonary evaluation including pulmonary function tests, chest radiographs, and BAL with analysis of cells, IgG, albumin, immune complexes, and fibronectin.nnnRESULTSnAlveolitis was detected on initial BAL evaluation in 21 patients (49%). Alveolitis was characterized by hypercellular lavage fluid, due to an absolute increase in alveolar macrophages and due to an increase in both the absolute number and percentage of granulocytes (neutrophils and eosinophils). Patients with systemic sclerosis had significantly higher levels of IgG and immune complexes in BAL fluid than did control subjects, and alveolar macrophages from patients with systemic sclerosis released higher amounts of fibronectin in vitro. In serial studies, alveolitis was found to persist. Patients with alveolitis had greater dyspnea than patients without alveolitis (p = 0.02), and they had greater reductions in lung volumes and carbon monoxide diffusing capacity (DLCO) (p = 0.004). Furthermore, patients with persistent alveolitis had significantly greater reductions in pulmonary function over time than patients without alveolitis (forced vital capacity [FVC]: -0.69 L versus -0.05 L, p less than 0.001; DLCO: -2.94 mL/minute/mm Hg versus +0.16 mL/minute/mm Hg, p = 0.03). BAL was used to select patients with alveolitis and at risk of pulmonary deterioration, and treatment was instituted with cyclophosphamide and prednisone, resulting in significant improvement in dyspnea (p less than 0.001) and the rate of change of FVC (p = 0.02) and DLCO (p less than 0.001).nnnCONCLUSIONnWe conclude that alveolitis occurs frequently in systemic sclerosis and that BAL is useful in identifying such patients who are at risk for a further decline in pulmonary status. Preliminary observations suggest that treatment of patients with active alveolitis may result in improvement in pulmonary status.

The histology of experimental pleural injury with tetracycline, empyema, and carrageenan

Models of pleural injury were established with intrapleural tetracycline, intrapleural carrageenan, and empyema in New Zealand White rabbits to evaluate histologically the pleural inflammatory response from 3 to 90 days. Both tetracycline and empyema models produced increases in the pleural connective tissue layers both above and below the fibroelastic membrane associated with angiogenesis and lymphangiogenesis. The influx of fibroblasts from the pleural surface into acellular fibrin strands formed adhesions between the visceral and the parietal pleurae. Injury to the mesothelial cell ranged from a cuboidal transition to total desquamation with the degree of mesothelial injury associated with the amount of fibrin adherence and the propensity toward fibrosis at 90 days. Intervention to promote the resolution of pleural inflammation without fibrosis should be directed toward preservation of the mesothelial surface, removal of pleural fibrin, and inhibition of fibroblast growth and chemotaxis.

Cocaine, pulmonary hemorrhage, and hemoptysis.

Excerpt To the Editor:We report a patient with recurrent massive hemoptysis and pulmonary hemorrhage temporally related to smoking freebase cocaine. A 20-year-old woman presented with massive hem...

Failure of the circulatory system limits exercise performance in patients with systemic sclerosis

OBJECTIVEnTo determine the mechanisms for exercise impairment in symptomatic patients with systemic sclerosis (SSc) using breath-by-breath expired-gas analysis with incremental exercise testing.nnnDESIGNnProspective, open trial.nnnPATIENTS AND METHODSnFifteen consecutive patients with SSc seen at the Medical University Hospital (a tertiary referral center) with complaints of exercise intolerance underwent pulmonary function testing (spirometry, helium dilution lung volumes, and diffusing capacity of carbon monoxide) and incremental exercise testing on a cycle ergometer measuring oxygen consumption (VO2), carbon dioxide production (VCO2), respiratory exchange ratio (R), oxygen saturation, blood pressure, and heart rate (HR). Values for oxygen uptake at anaerobic threshold (VO2AT) were derived graphically by blinded clinicians experienced in exercise testing, and the results were averaged. Ventilatory reserve and oxygen pulse were calculated from measured values, and all data were subjected to analysis by standard clinical algorithms.nnnMEASUREMENTS AND MAIN RESULTSnOf 15 patients studied, 14 had either restrictive lung disease or normal results of spirometry on pulmonary function testing. One patient with a history of tobacco use had evidence of airways obstruction. Three patients were unable to exercise maximally (as determined by maximum respiratory exchange ratio [Rmax] greater than 1.09 or maximum heart rate [HRmax] greater than 85% predicted), and exercise testing was terminated in one with Mobitz type II atrioventricular block. The following data (mean +/- SEM) were obtained from 11 maximally exercising patients: VO2max 795 +/- 75 mL oxygen (O2)/min, R 1.34 +/- 0.05, VO2AT/VO2max predicted 0.21 +/- 0.02, O2 pulse 5.1 +/- 0.4 mL O2/beat, ventilatory reserve 0.52 +/- 0.06, and tidal volume/forced vital capacity ratio 0.46 +/- 0.02. Of the 11 patients completing breath-by-breath expired-gas analysis, all had circulatory impairment to exercise, as determined by low O2 pulse and low VO2 at anaerobic threshold, and circulatory impairment was limiting in 9 of 11 patients. Of those nine patients, four had evidence of impaired gas exchange compatible with pulmonary vascular disease. Arterial oxygen desaturation occurred in 2 of 11 patients.nnnCONCLUSIONnCirculatory impairment to exercise is common in SSc patients with exercise intolerance. Restrictive lung disease, although also common, does not limit exercise tolerance in patients capable of maximal effort.