Biological lung volume reduction: a new bronchoscopic therapy for advanced emphysema.

BACKGROUND: Biological lung volume reduction (BLVR) using biological reagents to remodel and shrink damaged regions of lung has previously been accomplished in sheep with experimental pulmonary emphysema. This report summarizes the initial clinical experience including a 3-month follow-up using this technique in humans. METHODS: An open-label phase 1 trial designed to evaluate the safety of BLVR in patients with advanced heterogeneous emphysema enrolled six patients. Of these, three patients received unilateral treatment at two pulmonary subsegments (group 1) and three patients received unilateral treatment at four pulmonary subsegments (group 2). The incidence of adverse events and changes in pulmonary function test results, symptoms, and exercise capacity were evaluated. RESULTS: The mean (+/- SD) age of the six men enrolled in the study was 66 +/- 5.7 years (age range, 57 to 73 years). BLVR was well tolerated in both treatment groups and was not associated with any serious complications. All patients were discharged from the hospital on posttreatment day 1. Although the primary purpose of the study was to examine safety, improvements were observed in mean vital capacity (+7.2 +/- 9.5%; range, -2% to + 19%), mean residual volume (RV) [-7.8 +/- 8.5%; range, + 1% to -22%], mean RV/total lung capacity ratio (-6.6 +/- 4.7%; range, -1% to -15%), mean 6-min walk distance (+14.5 +/- 18.5%; range, 0 to + 51%), and in mean dyspnea score. On average, group 2 patients experienced greater benefit from BLVR than group 1 patients, suggesting a dose-response pattern. CONCLUSIONS: Preliminary results indicate that BLVR can be safe and may produce benefits in appropriately selected patients with advanced heterogeneous emphysema.

Systemic cytokines, clinical and physiological changes in patients hospitalized for exacerbation of COPD.

BACKGROUND: Systemic inflammation in patients with COPD may worsen during exacerbations, but there is limited information relating levels of systemic inflammatory markers with symptoms and physiologic changes during an exacerbation METHODS: We measured dyspnea using the visual analog scale, pulmonary function tests, hemograms, and plasma levels for interleukin (IL)-6, IL-8, leukotriene B(4) (LTB4), tumor necrosis factor-alpha, and secretory leukocyte protease inhibitor (SLPI) in 20 patients on admission to a hospital for exacerbation of COPD (ECOPD), 48 h later (interim), and 8 weeks after hospital discharge (recovery). RESULTS: Dyspnea was present in all patients. Inspiratory capacity improved faster than FEV(1). Compared to recovery, there was a significant increase in the mean (+/- SD) hospital admission plasma levels of IL-6 (6.38 +/- 0.72 to 2.80 +/- 0.79 pg/mL; p = 0.0001), IL-8 (8.18 +/- 0.85 to 3.72 +/- 0.85 pg/mL; p = 0.002), and LTB4 (8,675 +/- 1,652 to 2,534 +/- 1,813 pg/mL; p = 0.003), and the percentages of segmented neutrophils (79 to 69%; p < 0.02) and band forms (7.3 to 1.0%; p < 0.01) in peripheral blood, with no changes in TNF-alpha and SLPI. There were significant correlations between changes in IL-6 (r = 0.61; p = 0.01) and IL-8 (r = 0.56; p = 0.04) with changes in dyspnea and levels of IL-6 (r = -0.51; p = 0.04) and TNF-alpha (r = -0.71; p < 0.02) with changes in FEV(1.) CONCLUSIONS: Hospitalized patients with ECOPDs experience significant changes in systemic cytokine levels that correlate with symptoms and lung function. An ECOPD represents not only a worsening of airflow obstruction but also increased systemic demand in a host with limited ventilatory reserve.

Cough and phlegm are important predictors of health status in smokers without COPD.

STUDY OBJECTIVES: The health-related quality of life of smokers without COPD and that of ex-smokers has not been defined. If abnormal, the role of small airways disease and that of cough and phlegm have never been evaluated. Therefore, the aim of the study was to explore whether the differences in quality of life between smokers and ex-smokers could be explained by cough and phlegm, differences in pulmonary function tests, or exercise capacity. DESIGN: Observational, prospective. SETTING: Pulmonary and Critical Care Division, COPD Center at St. Elizabeth's Medical Center. POPULATION: In 36 smokers, 21 ex-smokers (stopped smoking for > 20 years), 19 never-smokers with normal FVC and FEV(1) values, and 41 patients with COPD (FEV(1) 38 +/- 11% predicted [mean +/- SD]), the St. George's Respiratory Questionnaire (SGRQ), pulmonary function tests, and a 6-min walk distance (6MWD) were performed. RESULTS: The total SGRQ scores were worse in current smokers (15 +/- 15) than in ex-smokers (6 +/- 4) or never-smokers (4 +/- 3) [p < 0.05]. As expected, the worst score was seen in COPD (50 +/- 15). After correcting for cough and phlegm, the difference in SGRQ scores between smokers and ex-smokers disappeared. In current and ex-smokers, the SGRQ score was associated with the exposure to pack-years smoking history (r = 0.45, p < 0.01, and r = 0.83, p < 0.0001, respectively) but independent of lung function or exercise parameters (6MWD). CONCLUSIONS: In smokers without COPD, the abnormal SGRQ score is due to the noxious effect of cigarette smoke, resulting in cough and phlegm, independent of its physiologic effects.

Muscle strength and exercise kinetics in COPD patients with a normal fat-free mass index are comparable to control subjects.

STUDY OBJECTIVE: This study was designed to investigate the extent of clinical muscle dysfunction in stable patients with COPD who were attending an out-patient pulmonary clinic compared with that of age-matched control subjects without COPD. DESIGN AND SUBJECTS: Respiratory muscle and hand grip strength, steady-state O(2) kinetics, and body composition were measured in 32 patients with COPD (19 women) [mean (+/- SD) FEV(1), 38 +/- 11% predicted] and 36 age-matched control subjects (13 women). RESULTS: Measurements of handgrip force (mean, 97 +/- 32% vs 106 +/- 26% predicted, respectively), maximal expiratory pressure (mean, 57 +/- 33% vs 61 +/- 22% predicted, respectively), steady-state O(2) kinetics (mean tau, 72 +/- 34 s vs 78 +/- 37 s, respectively) and steady-state CO(2) kinetics (mean tau, 77 +/- 38 s vs 65 +/- 32 s, respectively) at submaximal exercise were similar in patients and control subjects. All the subjects, except for one female COPD patient, had a normal fat-free mass index (FFMI), although on average the FFMI was lower in male patients (19.8 +/- 2.8) than in male control subjects (23.0 +/- 2.8; p < 0.01). CONCLUSIONS: In patients with COPD who were attending a regular outpatient pulmonary clinic, there was no evidence of reduced upper extremity and expiratory muscle strength or prolonged O(2) and CO(2) kinetics during isowork submaximal cardiopulmonary exercise compared to healthy, age-matched control subjects. Also, a normal body composition was found in nearly all COPD patients. This argues against the existence of a clinically significant systemic myopathy in most stable patients with severe COPD and normal FFMI.

Fatal acute interstitial pneumonitis complicating polymyositis in a 41-year-old man.

We report a case of a previously healthy 41-year-old man who was admitted for progressive dyspnea and cough, which culminated in respiratory failure, shock, and death. Lung and muscle biopsy results were consistent with interstitial lung disease secondary to polymyositis. Polymyositis and dermatomyositis are rare autoimmune diseases that primarily affect the muscles and skin, with frequent extramuscular and specifically pulmonary manifestations. Respiratory complications are in 2 categories: primary (the interstitial lung diseases, which can be acute or chronic) and secondary (aspiration pneumonia/pneumonitis, muscle weakness, infection, drug-induced disease, pulmonary congestion secondary to heart failure, pulmonary hypertension, and pneumomediastinum). Diagnosis of a specific interstitial lung disease relies mainly on high-resolution computed tomography of the chest and on tissue diagnosis. Prognosis depends on the histopathology findings and the specific form of interstitial lung disease and its response to therapy, which consists of high-dose steroids and immunomodulating agents. Unfortunately, patients with polymyositis/dermatomyositis associated with pulmonary complications have a worse prognosis than patients with isolated forms.