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Pulmonary capillaritis is defined as a histopathologic pattern of alveolar wall inflammation that leads to the disruption of the integrity of alveolar-capillary basement membranes and flooding of the alveoli with blood. The clinical presentation is that of diffuse alveolar hemorrhage (DAH). Pulmonary capillaritis is usually the consequence of an underlying immune-mediated process that is systemic in nature. Rarely, pulmonary capillaritis occurs in isolation. This article outlines a systematic approach to the management of patients presenting with DAH, and provides an overview of specific causes of pulmonary capillaritis.

Testing for antineutrophil cytoplasmic antibodies (ANCA) reacting with proteinase 3 (PR3) is part of the routine diagnostic evaluation of patients with small vessel vasculitis. For PR3-ANCA detection, capture ELISAs are reported to be superior to direct ELISAs. Standard capture ELISAs, in which PR3 is anchored by anti-PR3 monoclonal antibodies (moAB), have two potential disadvantages. First, the capturing moAB may compete for epitopes recognized by some PR3-ANCA, causing occasional false-negative results. Second, the capture of recombinant PR3 mutant molecules becomes unpredictable as modifications of specific conformational epitopes may not only affect the binding of PR3-ANCA, but also the affinity of the capturing anti-PR3 moAB. Here, we describe a new capture ELISA, and its application for PR3-ANCA detection. This new assay is based on the standardized capture of a variety of different carboxy-terminally c-myc tagged recombinant ANCA target antigens using anti-c-myc coated ELISA plates. Antigen used include c-myc tagged human rPR3 variants (mature and pro-form conformations), mouse mature rPR3 and human recombinant neutrophil elastase. This new anti-c-myc-capture ELISA for PR3-ANCA detection has an intra- and inter-assay coefficient of variation of 3.6% to 7.7%, and 15.8% to 18.4%, respectively. The analytical sensitivity and specificity for PR3-ANCA positive serum samples were 93% and 100%, respectively when rPR3 with mature conformation was used as target antigen, and 83% and 100% when the pro-enzyme conformation was employed. In conclusion, this new anti-c-myc capture ELISA compares favorably to our standard capture ELISA for PR3-ANCA detection, enables the unified capture of different ANCA target antigens through binding to a c-myc tag, and allows capture of rPR3 mutants necessary for PR3-ANCA epitope mapping studies.

Aspergillus osteomyelitis of the spine with acute diskitis has been well documented in immunocompromised hosts but is rare in immunocompetent patients. Predisposing factors to infection are prolonged neutropenia, hematologic malignancies, chemotherapy, history of prior spinal trauma or surgery, allograft transplantation, or any condition requiring the use of long-term immunosuppressive agents or systemic corticosteroids. Patients with chronic obstructive pulmonary disease (COPD) treated with systemic corticosteroids for either long-term management or frequent exacerbations are at potential risk for such infections. Patients with severe COPD treated primarily with inhaled corticosteroids are considered immunocompetent. This report describes 2 cases of Aspergillus osteomyelitis with acute diskitis in apparently immunocompetent patients with COPD who, aside from brief courses of systemic corticosteroids, were using inhaled corticosteroid therapy. One patient was treated with intravenous amphotericin B alone, whereas the other received amphotericin B and underwent surgical debridement. Both have done well and were symptom free at 6-month follow-up.

Introduction: A reduced diffusing capacity of the lung for carbon monoxide (DLCO) measured during a pulmonary function test can suggest pulmonary arterial hypertension (PAH). The DLCO has been reported to weakly correlate with pulmonary hemodynamics. Objective: To determine whether the relationship between the DLCO and pulmonary arterial pressures can be strengthened by normalizing the DLCO to spirometric variables. Patient and Methods: Patients were seen at a tertiary care referral center. Consecutive subjects who underwent right heart catheterization (RHC) for the evaluation of suspected PAH from 01 January 1991 through 01 October 2006 were identified. Pulmonary function testing (PFT) data performed within 60 days of the RHC was collected. Spearman rank correlation between PFT and RHC variables was calculated. Results: One hundred thirty-eight patients who had an RHC performed had complete PFTs available. No significant correlation was identified between the mean pulmonary artery pressure and the pulmonary vascular resistance against the DLCO, nor the DLCO when normalized to: forced expiratory volume in 1 s, forced vital capacity, total lung capacity or alveolar volume. Spirometric subgroups were identified by standard definitions of restrictive and/or obstructive ventilatory defects. Clinical subgroups were classified based on the clinically diagnosed cause of the patient's PAH. Again, no significant correlation was identified between the PFT variables and RHC measurements in these stratified subgroups. Conclusion: In patients with suspected PAH, invasive hemodynamic measurements of PAH do not correlate with PFT variables, even when corrected for spirometric volumes, and regardless of the subgroup of ventilatory physiology or clinical diagnosis. Please cite this paper as: Arunthari V, Burger CD and Lee AS. Correlation of pulmonary function variables with hemodynamic measurements in patients with pulmonary arterial hypertension. Clin Respir J 2011; 5: 35–43.

Background The pathogenic significance of antineutrophilic cytoplasmic antibodies (ANCA) in Wegener's granulomatosis is controversial. Their presence is influenced by the extent, severity, and activity of the disease at the time of sampling. The objective of this study was to determine the frequency of ANCA in patients with active Wegener's granulomatosis and to assess the influence of disease severity on test results. Methods Baseline serum samples from the 180 participants in a multicentric prospective trial were tested for ANCA by indirect immunofluorescence, direct enzyme-linked immunosorbent assay (ELISA), and capture ELISA. Disease activity was measured using the Birmingham Vasculitis Activity Score for Wegener's granulomatosis. All patients had active disease at enrollment. Patients were categorized as having severe (n=128) or limited (n=52) Wegener's granulomatosis. Results When all ANCA detection methods were combined, 166 patients (92%) were ANCA positive, including 96% with severe disease and 83% with limited disease. Conclusion ANCA are detectable in nearly all patients with active severe Wegener's granulomatosis, but approximately 1 of 5 patients with active limited disease are ANCA negative. Immunofluorescence and both direct and capture ELISAs are required for optimal detection, suggesting that ANCA are not recognized equally well by all testing methods.

Summary Objective To assess the frequency of cystic lung disease suggestive of pulmonary lymphangiomyomatosis in men with tuberous sclerosis complex. Patients and methods Retrospective review of CT scans of the chest and abdomen on 29 men with tuberous sclerosis complex encountered during a 13-year period, 1998 to 2010. Results Cystic lung disease (defined as ≥4 cysts) was seen in 11 of 29 men (38%) with tuberous sclerosis complex. The mean age of those with cystic lung disease was 46.3 ± 19.1 years. None of the patients had experienced pneumothorax or chylothorax and none had undergone a lung biopsy for evaluation of cystic lung disease. Lymphangiomyomatosis had been diagnosed in two of 11 patients with cystic lung disease. Renal angiomyolipomas were demonstrated in 14 of 25 patients (56%) with renal imaging available; all 14 had multiple bilateral renal involvement. In this limited cohort of patients, the presence of cystic lung disease did not correlate with age, smoking exposure or the presence of renal AMLs. Conclusion We conclude that tuberous sclerosis complex -related lymphangiomyomatosis may not be rare in men but is milder in severity.