Diffuse alveolar haemorrhage as a rare complication of antiphospholipid syndrome.

Diffuse alveolar haemorrhage (DAH) is a rare complication of antiphospholipid syndrome. With a mortality rate of 46%, early diagnosis and management remain an ongoing challenge. Case reports are limited, and management guidelines are not yet definitive. In this case report, we present a 43-year-old male with DAH who required high-dose oral steroids, intravenous methylprednisolone cyclophosphamide and rituximab over 18 months to control life-threatening episodes of pulmonary bleeding.

Pulmonary embolism: clinical presentation and diagnosis in the oldest old.

The incidence of pulmonary embolism (PE) in the oldest old (persons aged ≥85) is increasing, but there are limited data on its clinical features and diagnosis. We performed a retrospective cohort study of 302 consecutive patients with confirmed PE and compared the oldest old to the young (aged <65) and the younger old (aged 65-84). The most common symptoms in the oldest old were dyspnoea (74.3%) and tachypnoea (71.4%), but the prevalence of chest pain decreased with advancing age. Delayed diagnosis was most common in the oldest old and was associated with increasing age, absence of dyspnoea, presence of cardiorespiratory disease and a higher Charlson Comorbidity index. Better age-specific diagnostic pathways are required in this population.

Changes in ventilation and perfusion following lower lobe endoscopic lung volume reduction (ELVR) with endobronchial valves in severe COPD.

BACKGROUND: We have previously reported significant improvements in ventilation and perfusion (VQ) and V/Q matching in the contralateral lung, especially the non-targeted lower zone in patients with severe COPD following upper lobe ELVR with endobronchial valves. However, V/Q changes after lower lobe ELVR have not been described. METHODS: Seven patients with lower lobe heterogeneous emphysema underwent unilateral lower lobe ELVR at Macquarie University Hospital. Lung function tests, 6-minute walk tests (6MWT), St George's Respiratory Questionnaire (SGRQ) and planar differential VQ scans were performed at baseline and at 1, 3 and 12 months post-ELVR. RESULTS: Compared to baseline, patients showed significant improvements in FEV1 (0.83 ± 0.09L-0.97 ± 0.12L, p < 0.05), 6MWD (200.33 ± 56.54 m-274.24 ± 48.03 m, p < 0.05) and SGRQ (61.13 ± 5.33-42.86 ± 6.99, p < 0.05) at 3 months after ELVR. This improvement was maintained at 12 months. There was a corresponding significant improvement in the differential ventilation (30.21 ± 3.04%-37.82 ± 3.76%, p < 0.05) and perfusion (31.77 ± 2.53%-35.60 ± 2.58%, p < 0.05) of the contralateral non-targeted upper zone. CONCLUSIONS: Within the limitations of a small sample size, we have found that in heterogeneous severe COPD patients undergoing ELVR targeting the lower lobes, there are clinical and PFT improvements similar to that reported in ELVR targeting upper lobes. Contralateral improvement in V/Q matching also occurs following lower lobe ELVR with the greatest improvement in the contralateral upper zone, suggesting the contralateral upper lobe should be the least affected lobe if the lower lobe is targeted in ELVR. These findings need to be confirmed in a study with a larger number of patients.

Endoscopic Lung Volume Reduction in COPD: Improvements in Gas Transfer Capacity Are Associated With Improvements in Ventilation and Perfusion Matching.

BACKGROUND: Endoscopic lung volume reduction (ELVR) has been shown to improve lung function, quality of life, and exercise tolerance in patients with severe heterogeneous emphysema. Our study aims to determine the effect of ELVR on gas transfer capacity corrected for alveolar volume (KCO) and investigate the relationship between KCO and ventilation and perfusion (VQ) matching. We speculate on possible mechanisms for the observed changes METHODS:: Patients with severe chronic obstructive pulmonary disease were prospectively recruited and underwent unilateral upper lobe ELVR between 2012 and 2014. Each had respiratory function test and differential VQ scans at baseline, 1-, 3-, and 12-month post-ELVR. RESULTS: In total, 11 patients had 3 sets of respiratory function test (at baseline, 1, and 3 mo), whereas 7 had 4 sets (at baseline, 1, 3, and 12 mo). KCO improved by 10.3 (±7.5)% at 1 month (P=NS) and 39.8 (±15.4)% at 12 months (P<0.05). VQ of the nontargeted lung increased by 12.8 (±5.6)% and 7.9 (±2.3)%, respectively at 1 month, whereas those of the targeted lung both decreased (P<0.05). At 3 and 12 months, the VQ changes were similar to those at 1 month, though some were not statistically significant. CONCLUSIONS: ELVR results in improved KCO for at least 12 months. This may be explained by the VQ redistribution to the nontargeted and less emphysematous lung with improved VQ matching.

Pathogenic profiles and molecular signatures of antinuclear autoantibodies rescued from NZM2410 lupus mice.

Two outstanding questions concerning antinuclear antibodies (ANAs) in lupus involve their pathogenic potential and their molecular signatures. To address these questions, a panel of 56 antinuclear and 47 nonnuclear binding monoclonal antibodies was rescued from four seropositive NZM2410 lupus mice. The monoclonals varied in their reactivity to nucleosomes, ssDNA, dsDNA, and glomerular substrate. A large fraction of the antibodies demonstrated apparent polyreactivity (to DNA, histones, and glomerular antigens) due to bound, DNase-1 sensitive nuclear antigenic bridges. Although nephrophilic immunoglobulin (Ig) M and IgG antibodies were the most pathogenic, the dsDNA-binding antibodies were modestly so; in contrast, antinucleosome antibodies were clearly not pathogenic. Compared with the nonnuclear antigen-binding monoclonal antibodies rescued from the same mice, ANAs exhibited increased utilization of VH5/7183 genes and highly cationic heavy chain (HC) CDR3 regions. Most intriguingly, the CDR3 regions of the ANAs exhibited alternating arginine/lysine peaks at H96, H98, and H100, with neutral troughs at H95, H97, and H99. To summarize, glomerular-binding anti-dsDNA antibodies appear to be the most pathogenic variety of lupus autoantibodies. The presence of an alternating charge pattern in their HC CDR3 regions appears to be a prominent hallmark of ANAs.

Molecular signatures of anti-nuclear antibodies--contribution of heavy chain framework residues.

It is clear that besides the CDR residues, framework residues (particularly those on FR1 and FR3) can contribute towards antigen reactivity. This study was designed to compare the immunoglobulin heavy chain FR regions of anti-nuclear antibodies (comprised of 142 anti-ssDNA, 103 anti-dsDNA and 23 anti-nucleosome Abs) with those of non-nuclear antibodies (N=165), all drawn from the GenBank. The anti-nuclear antibodies depicted residue-usage differences that reached statistical significance in their FR1 (at H1 and H29), FR2 (at H40), and FR3 (at H69, H73, H76, H80 and H87) regions. Interestingly, these residue-usage differences were intimately linked to differences in the usage frequencies of different V(H) germline genes between the different groups of antibodies; thus, whereas J558.4, J558.47, J558.m, and 7183.9 germline genes were over-utilized among the ANAs, J558.17, V130, V(H) 36-60 and VGk1a were over-represented among the non-ANAs. In conclusion, although the framework regions of ANAs exhibited distinctly different residue-usage patterns, they may simply be markers of associated germline-encoded CDR differences that appear to have been co-selected. Further studies are warranted to ascertain if any of the observed framework residue differences do actually contribute to nuclear antigen reactivity.