James P. Utz

Treatment of idiopathic pulmonary fibrosis with etanercept: an exploratory, placebo-controlled trial.

RATIONALE An efficacious medical therapy for idiopathic pulmonary fibrosis (IPF) remains elusive. OBJECTIVES To explore the efficacy and safety of etanercept in the treatment of IPF. METHODS This was a randomized, prospective, double-blind, placebo-controlled, multicenter exploratory trial in subjects with clinically progressive IPF. Primary endpoints included changes in the percentage of predicted FVC and lung diffusing capacity for carbon monoxide corrected for hemoglobin (Dl(CO(Hb))) and change in the alveolar to arterial oxygen pressure difference P(a-a)(O(2)) at rest from baseline over 48 weeks. MEASUREMENTS AND MAIN RESULTS Eighty-eight subjects received subcutaneous etanercept (25 mg) or placebo twice weekly as their sole treatment for IPF. No differences in baseline demographics and disease status were detected between treatment groups; the mean time from first diagnosis was 13.6 months and mean FVC was 63.9% of predicted. At 48 weeks, no significant differences in efficacy endpoints were observed between the groups. A nonsignificant reduction in disease progression was seen in several physiologic, functional, and quality-of-life endpoints among subjects receiving etanercept. There was no difference in adverse events between treatment groups. CONCLUSIONS In this exploratory study in patients with clinically progressive IPF, etanercept was well tolerated. Although there were no differences in the predefined endpoints, a decreased rate of disease progression was observed on several measures. Further evaluation of TNF antagonists in the treatment of IPF may be warranted. Clinical trial registered with www.clinicaltrials.gov (NCT 00063869).

High short-term mortality following lung biopsy for usual interstitial pneumonia

Usual interstitial pneumonia (UIP) is a specific histological pattern of interstitial pneumonia most often associated with the clinical syndrome of idiopathic pulmonary fibrosis (IPF). There is controversy regarding the use of surgical lung biopsy in the diagnosis of UIP, and the risk of lung biopsy in these patients is largely unknown. This study investigated the 30 day surgical mortality rate in patients undergoing surgical lung biopsy for UIP. Patients undergoing surgical lung biopsy over a 10-yr period from 1986-1995 with the ultimate diagnosis of UIP (with or without underlying connective tissue disease) were identified. Pathology, computed tomography, medical records, and survival were assessed. Ten of sixty patients with usual interstitial pneumonia were found to be dead within 30 days of surgical biopsy. All of these were patients with idiopathic UIP, unassociated with connective tissue disease (clinical condition of IPF). In conclusion, patients with usual interstitial pneumonia of the idiopathic type, who present with atypical features, may be at higher risk for death following surgical biopsy than patients presenting with more typical features or patients with other interstitial illnesses.

Idiopathic Pulmonary Fibrosis: Evolving Concepts

Idiopathic pulmonary fibrosis (IPF) occurs predominantly in middle-aged and older adults and accounts for 20% to 30% of interstitial lung diseases. It is usually progressive, resulting in respiratory failure and death. Diagnostic criteria for IPF have evolved over the years, and IPF is currently defined as a disease characterized by the histopathologic pattern of usual interstitial pneumonia occurring in the absence of an identifiable cause of lung injury. Understanding of the pathogenesis of IPF has shifted away from chronic inflammation and toward dysregulated fibroproliferative repair in response to alveolar epithelial injury. Idiopathic pulmonary fibrosis is likely a heterogeneous disorder caused by various interactions between genetic components and environmental exposures. High-resolution computed tomography can be diagnostic in the presence of typical findings such as bilateral reticular opacities associated with traction bronchiectasis/bronchiolectasis in a predominantly basal and subpleural distribution, along with subpleural honeycombing. In other circumstances, a surgical lung biopsy may be needed. The clinical course of IPF can be unpredictable and may be punctuated by acute deteriorations (acute exacerbation). Although progress continues in unraveling the mechanisms of IPF, effective therapy has remained elusive. Thus, clinicians and patients need to reach informed decisions regarding management options including lung transplant. The findings in this review were based on a literature search of PubMed using the search terms idiopathic pulmonary fibrosis and usual interstitial pneumonia, limited to human studies in the English language published from January 1, 2000, through December 31, 2013, and supplemented by key references published before the year 2000.

Mediastinoscopy in Patients With Lung Cancer and Negative Endobronchial Ultrasound Guided Needle Aspiration

BACKGROUND Endobronchial ultrasound with transbronchial needle aspiration (EBUS-TBNA) has been proposed as a safe, less-invasive alternative to mediastinoscopy to stage mediastinal lymph nodes in patients with lung cancer. We evaluated the negative predictive value of EBUS-TBNA in lung cancer patients suspected of having N2 nodal metastases. METHODS This study is a single-institution retrospective review of cases with suspected or confirmed lung cancer undergoing mediastinoscopy after a negative EBUS-TBNA between June 2006 and February 2008. RESULTS A total of 494 patients underwent EBUS-TBNA during the study period. Twenty-nine patients with suspected or confirmed lung cancer had a negative EBUS-TBNA and underwent subsequent mediastinoscopy. Mediastinoscopy was performed for findings suspicious of N2 disease based on noninvasive imaging. Mediastinoscopy found metastatic nodes in eight of 29 patients (28%) for a patient-specific negative predictive value of EBUS-TBNA of 72% (95% CI, 56% to 89%). Mediastinal lymph node dissection found four further patients with positive N2 nodes (19%). The EBUS-TBNA and mediastinoscopy sampled the same lymph node station on 36 occasions in the 29 patients. The average lymph node size was 10 mm. Mediastinoscopy was positive in 5 of 36 stations, for a nodal-specific negative predictive value of EBUS-TBNA of 86% (95% CI, 75% to 97%). CONCLUSIONS Endobronchial ultrasound with transbronchial needle aspiration can effectively sample mediastinal lymph node stations in patients with lung cancer. However, in this early experience, 28% of patients with high clinical suspicion of nodal disease had N2 mediastinal nodal metastases confirmed by mediastinoscopy despite negative EBUS-TBNA.

Lung Volume Reduction Surgery for Emphysema: Out on a Limb Without a NETT

Lung volume reduction surgery (LVRS) has recently been rediscovered and offers the potential of improving the quality of life of patients with advanced emphysema. In this article, we discuss the historical and contemporary versions of LVRS. Although initial enthusiasm has been substantial, existing data seem insufficient to demonstrate the safety and efficacy of the procedure in comparison with conventional medical therapy. Fundamental questions remain regarding the long-term effects of an operation versus medical therapy, the optimal selection criteria, the best measures of efficacy, the mechanisms of improvement, the cost-effectiveness of the procedure, and the optimal surgical technique. Until such questions are answered, advising patients about the best management their emphysema will be difficult. The National Emphysema Treatment Trial will address many of these issues and should be embraced by both health-care providers and patients.

Interferon Gamma-1b Therapy for Advanced Idiopathic Pulmonary Fibrosis

OBJECTIVE To report on observations made in a group of patients with idiopathic pulmonary fibrosis/usual interstitial pneumonia (IPF/UIP) who were treated with interferon gamma-1b. PATIENTS AND METHODS We reviewed the clinical records, radiological studies, and pulmonary function data of all patients treated with interferon gamma-1b between January 2000 and March 2002 at the Mayo Clinic in Rochester, Minn. RESULTS Twenty-one patients (mean age, 68 years; range, 52-80 years) were treated with interferon gamma-1b for a mean duration of 82 months (range, 3-21 months). All patients had been diagnosed previously as having IPF/UIP based on clinical, pulmonary function, and chest high-resolution computed tomographic scan criteria; 12 patients had also undergone video-assisted thoracoscopic surgical lung biopsy. Baseline pulmonary function data (mean +/- SEM percent predicted) were as follows: total lung capacity, 57.3 +/- 2.5; vital capacity, 55.0 +/- 3.3; diffusing capacity of lung for carbon monoxide, 39.7 +/- 2.8; and forced expiratory volume in 1 second, 58.1 +/- 3.6. Only 1 patient showed symptomatic and functional improvement, and 7 discontinued treatment because of a perceived lack of benefit. Eleven patients (52%) died after a mean of 6.4 months of treatment, and follow-up pulmonary function data suggested continued worsening in all but 1 patient. CONCLUSION These observations do not support the use of interferon gamma-lb therapy for patients with advanced IPF/UIP.

Airway foreign bodies in adults

The objective of this study was to evaluate the efficacy of flexible bronchoscopy in the management of tracheobronchial foreign bodies (TFB) in adults (≥16 y) from 1990 through 2002. TFB was defined as the presence of any foreign object below the vocal cords. Patients with gastric aspiration or regurgitation were excluded. We reviewed Mayo Clinic Rochesters medical data retrieval system to obtain information on patients with TFBs. Data abstracted included demographics, clinical symptoms, physical examination findings, bronchoscopic techniques used for extraction, success rates, and complications. A total of 65 adults with TFB aspiration were identified. There were 44 males (68%) and 21 females (32%) with a mean age of 60.8 years. A recognized predisposition to aspiration was evident in 35 patients (54%). The right lower lobe was the most common site for lodgment of aspirated TFB (24 of 65 patients; 37%), followed by the bronchus intermedius in 14 patients (22%), trachea in 7 (11%), left main stem bronchus in 7 (11%), and other locations in the rest. The most common symptom was cough (58 of 65 patients; 89%). The most common finding on physical examination was wheezing, seen in 20 patients (31%). Chest radiographs were obtained in 59 patients (91%) and were abnormal in 54 (92%). TFB was seen or its presence was suggested on the chest radiograph in 19 patients (32%). TFBs extracted included dental pieces in 14 patients (22%), nuts in 12 (18%), corn kernels in 7 (11%), vegetable matter in 7 (11%), bones in 6 (9%), plastic pieces in 4 (6%), pills in 2 (3%), and one each of the following: meat, nail, laryngeal polyp, folded drinking straw, broken piece of an endotracheal tube, broken piece of a voice prosthesis, tracheostomy cleaning brush, foil, surgical staple, surgical pledget, balloon fragment, sunflower seed, and a sewing needle. The flexible bronchoscope was used in 61 of the 65 patients (94%) and was successful in 54 of these patients (89%). Flexible bronchoscopy was unsuccessful in 7 patients, 6 of whom underwent successful TFB extraction by rigid bronchoscopy. One patient required a thoracotomy for the removal of a TFB in the right lower lobe. Complications from bronchoscopy were minimal and consisted of minor bleeding in 3 patients. Flexible bronchoscopic procedures were successful in the extraction of 89% of tracheobronchial foreign bodies in adults. Our experience also indicates that flexible bronchoscopic removal of TFBs in adults can be safely performed with minimal complications.

External-Beam Radiation Therapy in the Treatment of Diffuse Tracheobronchial Amyloidosis

Tracheobronchial amyloidosis is characterized by deposits of amyloid in airway walls. No effective treatment is known. We describe a 59-year-old woman who presented with increasing symptoms of airway obstruction due to diffuse deposition of amyloid throughout her tracheobronchial tree. She was treated with external-beam radiation therapy (20 Gy) with marked improvement in her symptoms, effort tolerance, bronchoscopic appearance, and forced expiratory volume in 1 second (1.39 L to 1.97 L [42%]). This improvement was maintained during 21 months of follow-up.

Risk of osteoporotic fractures in women with breast cancer: A population-based cohort study

A population-based study was undertaken to assess the risk of osteoporotic fractures in an inception cohort of breast cancer patients and an age-matched cohort of women from the community. Prior to the index date, 9.4% of cases and 12.3% of controls (p = 0.30) had one or more osteoporotic fractures. After the index date, these proportions were 16.2 and 20.0% (p = 0.28), but follow-up was shorter for cases due to reduced survival. When duration of follow-up was accounted for in a person-years analysis, the relative risk of any fracture was 1.0 and for any osteoporotic fracture was 0.9 (95% C.I. 0.7-1.2). After adjusting for other factors in a proportional hazards model, the relative risk of any osteoporotic fracture in breast cancer cases compared to controls was 0.9. Despite contentions that breast cancer patients have more often been exposed to estrogenic factors, we found little to suggest that such women are substantially protected from osteoporotic fractures.

IgG4-Related Systemic Disease Presenting With Lung Entrapment and Constrictive Pericarditis

We describe a 29-year-old woman who presented with chronic pleuropericarditis complicated by lung entrapment and constrictive pericarditis. Pleural biopsy performed during the decortication procedure revealed fibrinous pleuritis with lymphoplasmacytic inflammation including IgG4-positive plasma cells. The patient responded favorably to corticosteroid therapy with resolution of pleural effusion and constrictive physiology. To our knowledge, this is the first reported case of IgG4-related systemic disease manifesting as lung entrapment and constrictive pericarditis.