E. James Britt

Comparison of the anticholinergic bronchodilator ipratropium bromide with metaproterenol in chronic obstructive pulmonary disease: A 90-day multi-center study

The short- and long-term efficacy and safety of an inhaled quaternary ammonium anticholinergic agent, ipratropium bromide, and a beta agonist aerosol, metaproterenol, were compared in 261 nonatopic patients with chronic obstructive pulmonary disease (COPD). The study was a randomized, double-blind, 90-day, parallel-group trial. On three test days-one, 45, and 90-mean peak responses for forced expiratory volume in one second and forced vital capacity and mean area under the time-response curve were higher for ipratropium than for metaproterenol. Clinical improvement was noted in both treatment groups, especially during the first treatment month, with persistence of improvement throughout the remainder of the study. Side effects were relatively infrequent and generally mild; tremor, a complication of beta agonists, was not reported by any subject receiving ipratropium. These results support the effectiveness and safety of long-term treatment with inhaled ipratropium in COPD.

Cryptogenic Hemoptysis: Clinical Features, Bronchoscopic Findings, and Natural History in 67 Patients

We reviewed the clinical outcome of 67 patients with hemoptysis and a normal or nonlocalizing chest roentgenogram and nondiagnostic fiberoptic bronchoscopic examination. During a 38 +/- 22 (SD) month period after bronchoscopy, 57 (85%) patients remained well without evidence of active tuberculosis or overlooked bronchogenic carcinoma, and 9 patients died of nonpulmonary conditions. One patient developed bronchogenic carcinoma 20 months after bronchoscopy and resolution of symptoms. Hemoptysis had resolved completely before hospital discharge in 38 (57%) patients, within 6 months in 60 (90%), and recurred in only 3. Five patients (7.5%) had intermittent episodes of bleeding for more than 1 year. Fiberoptic bronchoscopy effectively excludes specific underlying causes of hemoptysis in the setting of a normal chest roentgenogram. The prognosis for patients with cryptogenic hemoptysis is generally good, usually with resolution of bleeding within 6 months of evaluation.

Acute bronchodilating effects of ipratropium bromide and theophylline in chronic obstructive pulmonary disease

The bronchodilator effects of a single dose of ipratropium bromide aerosol (36 micrograms) and short-acting theophylline tablets (dose titrated to produce serum levels of 10-20 micrograms/mL) were compared in a double-blind, placebo-controlled crossover study in 21 patients with stable, chronic obstructive pulmonary disease. Mean peak forced expiratory volume in 1 second (FEV1) increases over baseline and the proportion of patients attaining at least a 15% increase in the FEV1 (responders) were 31% and 90%, respectively, for ipratropium and 17% and 50%, respectively, for theophylline. The average FEV1 increases during the 6-hour observation period were 18% for ipratropium and 8% for theophylline. The mean duration of action was 3.8 hours with ipratropium and 2.4 hours with theophylline. While side effects were rare, those experienced after theophylline use did involve the cardiovascular and gastrointestinal systems. These results show that ipratropium is a more potent bronchodilator than oral theophylline in patients with chronic airflow obstruction.

Lymphocyte aggregates persist and accumulate in the lungs of patients with idiopathic pulmonary fibrosis

Background Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease with no known effective therapy. It is often assumed, but has not been objectively evaluated, that pulmonary inflammation subsides as IPF progresses. The goal of this work was to assess changes in the degree of inflammatory cell infiltration, particularly lymphocytic infiltration, over the duration of illness in IPF. Methods Sixteen patients with confirmed IPF were identified in patients whom surgical lung biopsy (SLB) was performed in early disease, and in patients whom lung transplantation was subsequently performed in end stage disease. A numerical scoring system was used to histologically quantify the amount of fibrosis, honeycomb change, fibroblastic foci, and lymphocyte aggregates in each SLB and lung explant tissue sample. Analyses of quantitative scores were performed by comparing paired, matched samples of SLB to lung explant tissue. Results Median time [1st, 3rd quartiles] from SLB to lung transplantation was 24 [15, 29] months. Histologic fibrosis and honeycomb change were more pronounced in the explant samples compared with SLB (P < 0.001 and P < 0.01, respectively), and most notably, higher numbers of lymphocyte aggregates were observed in the explant samples compared to SLB (P = 0.013). Immunohistochemical analyses revealed abundant CD3+ (T lymphocyte) and CD20+ (B lymphocyte) cells, but not CD68+ (macrophage) cells, within the aggregates. Conclusion Contrary to the frequent assumption, lymphocyte aggregates were present in greater numbers in advanced disease (explant tissue) compared to early disease (surgical lung biopsy). This finding suggests that active cellular inflammation continues in IPF even in severe end stage disease.

Pulmonary T cell repertoire in patients with graft-versus-host disease following blood and marrow transplantation.

Pulmonary inflammation is one of the risk factors associated with blood and marrow transplantation (BMT). To determine the potential role of T cells in pulmonary complications after transplantation, we analyzed the T‐cell repertoire expressed in bronchoalveolar lavage fluids from eleven patients with graft‐versus‐host disease following BMT. A reverse transcriptase‐polymerase chain reaction was used to amplify rearranged TCR transcripts in unfractionated, CD4+, and CD8+ T cells from bronchoalveolar lavage fluids. The relative expression of TCR variable (V) gene families and the diversity of junctional region lengths associated with different AV and BV gene families were analyzed. Nearly all TCR AV and BV gene families were detected in bronchoalveolar lavage cells from BMT recipients. Oligoclonal patterns of TCR junctional region lengths were observed in unfractionated, CD4+, and CD8+ bronchoalveolar T cells. The oligoclonal expansion of bronchoalveolar T cells in patients was confirmed by DNA sequencing. TCRV gene expression is almost completely restored in the lungs of BMT recipients as early as two weeks after transplantation. Increased oligoclonality among TCR gene families suggests either an incomplete restoration of TCR diversity or an antigen‐driven expansion of T cells in the lungs of BMT recipients with graft‐versus‐host disease, not necessarily related to pulmonary infection. Am. J. Hematol. 66:1–11, 2001.