The burden of idiopathic pulmonary fibrosis: an unmet public health need.

Idiopathic pulmonary fibrosis (IPF) is a fibrotic lung disease of unknown cause characterized by relentlessly progressive restrictive-ventilatory limitation, hypoxia, dyspnea, and cough. Both the incidence and prevalence of IPF appears to be increasing, with little impact on its dismal 3-year median survival, despite two decades of clinical trials. Increasingly recognized are the serious associated comorbid illnesses, including pulmonary hypertension, chronic obstructive pulmonary disease, gastroesophageal reflux disease, obstructive sleep apnea, obesity, lung cancer, and depression that further contribute to the substantial rise in the use of IPF-related healthcare resources. At present, lung transplantation remains the sole viable treatment for the few who qualify. Pharmacologic interventions targeting lung function and survival have remained largely disappointing, and very few investigations have specifically targeted comorbid conditions, symptoms, quality-of-life, and healthcare resource utilization. In reviewing the burden of illness associated with IPF, including the epidemiology, comorbidities, quality-of-life and the physical, psychosocial, and economic costs of this devastating disease, we hope to highlight some of the unmet medical needs associated with IPF, and encourage both public support and further investigations into these and other patient-centered outcomes and not just that of survival and lung function.

Morphologic and quantitative assessment of CD20+ B cell infiltrates in rheumatoid arthritis-associated nonspecific interstitial pneumonia and usual interstitial pneumonia.

OBJECTIVE: B lymphocytes are emerging as important elements in the events leading to joint destruction in rheumatoid arthritis (RA). However, B lymphocytes have not been studied in rheumatoid arthritis (RA)-associated lung disease. We performed a morphologic and quantitative analysis of B lymphocytes and plasma cells in RA-associated interstitial pneumonia (IP) in comparison with idiopathic IP and normal lungs. METHODS: Open-lung biopsy specimens from patients with RA-associated IP (n = 18), patients with idiopathic IP (n = 21), and control subjects (n = 11) were stained with antibodies to CD20 and CD138. Morphologic patterns of stained specimens were characterized and staining was quantified using computer-assisted image analysis. RESULTS: In RA-associated IP, marked follicular B cell hyperplasia was detected, which was limited almost entirely to peribronchiolar lymphoid aggregates. Plasma cells were also present in large numbers, but showed a more diffuse tissue infiltration. Quantification of B cells demonstrated higher cellularity in RA-associated IP (median 2.0%, interquartile range [IQR] 1.0-5.7) as compared with idiopathic IP (0.9%, IQR 0.5-2.1). Control specimens showed a significantly smaller number of B cells compared with both diseases (0.4%, IQR 0.1-1.3). In RA patients who were smokers and in those who were male, the proportion of CD20+ tissue areas further increased to 4.3% (IQR 1.0-5.8) and 3.9% (IQR 0.7-6.9), respectively. CONCLUSION: We demonstrated a significant follicular B cell hyperplasia in RA-associated IP. The differences between RA-associated IP and idiopathic IP imply a differential emphasis of B cell-mediated mechanisms in the 2 diseases despite radiologic and histologic similarities and provide a rationale for studying functional aspects of B cell involvement in the pathogenesis of RA-associated IP.

Outcomes after withholding anticoagulation from patients with suspected acute pulmonary embolism and negative computed tomographic findings: a cohort study.

OBJECTIVE: To determine the outcome of withholding anticoagulation from patients with suspected acute pulmonary embolism in whom computed tomographic (CT) findings are interpreted as negative for pulmonary embolism. PATIENTS AND METHODS: This retrospective cohort study included 1512 consecutive patients referred from August 7, 1997, to November 30, 1998, for CT because of clinically suspected acute pulmonary embolism. All patients were examined by electron beam CT, and scanning was performed in a cephalocaudad direction from the top of the aortic arch to the base of the heart with 3-mm collimation, 2-mm table incrementation, and an exposure time of 0.2 second (130 peak kV, 620 mA, and standard reconstruction algorithm). Contrast material was infused at a rate of 3 to 4 mL/s through an antecubital vein with an automated injector. Findings on CT were interpreted as either positive or negative. The main outcome measures were deep venous thrombosis, pulmonary embolism, and vital status within 3 months after the CT scan and the cause of death based on medical record review, mailed patient questionnaires, and telephone interviews. RESULTS: In 1010 patients (67%) CT scans were interpreted as negative for acute pulmonary embolism. Seventeen patients were excluded because they received anticoagulation. Of the remaining 993 patients, deep venous thrombosis or pulmonary embolism developed in 8; 118 patients died, 3 of pulmonary embolism. Nineteen patients were known to be alive, but additional clinical information could not be obtained. The 3-month cumulative incidence of overall deep venous thrombosis or pulmonary embolism was 0.5% (95% confidence interval, 0.1%-1.0%) and of fatal pulmonary embolism, 0.3% (95% confidence interval, 0.0%-0.7%). CONCLUSIONS: The incidence of (1) overall deep venous thrombosis or pulmonary embolism or (2) fatal pulmonary embolism among patients with suspected acute pulmonary embolism, negative CT results, and no other evidence of venous thromboembolism is low. Withholding anticoagulation in these patients appears to be safe.