Judith Babar

Clinical spectrum and features of activated phosphoinositide 3-kinase δ syndrome: A large patient cohort study

Background: Activated phosphoinositide 3‐kinase &dgr; syndrome (APDS) is a recently described combined immunodeficiency resulting from gain‐of‐function mutations in PIK3CD, the gene encoding the catalytic subunit of phosphoinositide 3‐kinase &dgr; (PI3K&dgr;). Objective: We sought to review the clinical, immunologic, histopathologic, and radiologic features of APDS in a large genetically defined international cohort. Methods: We applied a clinical questionnaire and performed review of medical notes, radiology, histopathology, and laboratory investigations of 53 patients with APDS. Results: Recurrent sinopulmonary infections (98%) and nonneoplastic lymphoproliferation (75%) were common, often from childhood. Other significant complications included herpesvirus infections (49%), autoinflammatory disease (34%), and lymphoma (13%). Unexpectedly, neurodevelopmental delay occurred in 19% of the cohort, suggesting a role for PI3K&dgr; in the central nervous system; consistent with this, PI3K&dgr; is broadly expressed in the developing murine central nervous system. Thoracic imaging revealed high rates of mosaic attenuation (90%) and bronchiectasis (60%). Increased IgM levels (78%), IgG deficiency (43%), and CD4 lymphopenia (84%) were significant immunologic features. No immunologic marker reliably predicted clinical severity, which ranged from asymptomatic to death in early childhood. The majority of patients received immunoglobulin replacement and antibiotic prophylaxis, and 5 patients underwent hematopoietic stem cell transplantation. Five patients died from complications of APDS. Conclusion: APDS is a combined immunodeficiency with multiple clinical manifestations, many with incomplete penetrance and others with variable expressivity. The severity of complications in some patients supports consideration of hematopoietic stem cell transplantation for severe childhood disease. Clinical trials of selective PI3K&dgr; inhibitors offer new prospects for APDS treatment.

Respiratory disease in common variable immunodeficiency and other primary immunodeficiency disorders

Respiratory disease is a significant cause of morbidity and mortality amongst patients with primary immunodeficiency disorders. Computed tomography (CT) plays an important role in the multidisciplinary approach to these conditions, in detecting, characterizing, and quantifying the extent of lung damage and in directing treatment. The aim of this review is to classify the primary immunodeficiency disorders and describe the thoracic complications and the associated CT findings whilst discussing the role of radiology in diagnosis and surveillance.

Acute lung injury results from failure of neutrophil de-priming: a new hypothesis

Eur J Clin Invest 2012; 42 (12): 1342–1349

Evolution of CT pulmonary angiography: referral patterns and diagnostic yield in 2009 compared with 2006

Background CT pulmonary angiography (CTPA) is an increasingly popular imaging test for assessing patients with acute chest pain. Purpose To evaluate the number of CTPA performed in 2009 compared with 2006 and assess the frequency of pulmonary embolus (PE) versus alternative diagnoses. Material and Methods Numbers of CTPA and V/Q scans performed in a six-month period of 2006 and 2009 were established by review of the hospital radiology information system. CTPAs were evaluated by two radiologists in consensus and the incidence of pulmonary embolism and alternative diagnoses in 2006 and 2009 were recorded. Results The final study groups were 99 patients who underwent CTPA in 2006 and 149 patients in 2009. There was a significant fall in the incidence of PE identified on CTPA in 2009 compared to 2006 (11% versus 21%, P = 0.04). There was a non-significant rise in the incidence of alternative diagnoses in 2009 compared to 2006 (45% versus 40%, P = 0.48). Nine types of alternative radiological diagnoses were made on CTPA, the most common of which was pneumonia in both time periods (17% and 12%). Eighty-seven V/Q scans were performed in the study period in 2006, compared to 109 in 2009. The incidence of PE identified on V/Q scanning remained stable (8% in 2009 versus 12% in 2006, P = 0.44). Conclusion The numbers of CTPAs being performed has increased in three years. The incidence of PE identified has fallen and there has been a modest increase in the number of alternative diagnoses.

A practical approach to cystic lung disease on HRCT

A lung cyst is defined as a round parenchymal lucency or area of low attenuation with a thin wall. They are not uncommon findings on high-resolution (HR) thoracic computed tomography (CT) and when identified, they require explanation. The differential diagnosis for diseases characterised by lung cysts is broad ranging from isolated chest disorders to rare multisystem diseases. This article provides a practical approach for evaluating lung cysts on HRCT, highlighting disorders in which the HRCT findings can be diagnostic as well as conditions where correlation with clinical history or biopsy is required.

Imaging of Congenital and Acquired Disorders of the Pulmonary Artery

The pulmonary artery is affected by a multitude of conditions that can be congenital or acquired. These disorders may be detected incidentally, or the clinical features of the different conditions may overlap. This pictorial review illustrates the imaging findings of some of the main conditions that affect the pulmonary artery by considering them in 3 main categories: congenital disorders; enlargement of the pulmonary arteries, most commonly seen in pulmonary hypertension; obstruction or occlusion of the pulmonary arteries, as seen in thromboembolic disease or large vessel vasculitis. It is important for the radiologist to understand the radiological manifestations of these disorders, as early recognition would be of significant benefit in their diagnosis and treatment.

Incidence and recognition of acute respiratory distress syndrome in a UK intensive care unit.

The reported incidence of ARDS is highly variable (2.5%–19% of intensive care unit (ICU) patients) and varies depending on study patient population used. We undertook a 6-month, prospective study to determine the incidence and outcome of ARDS in a UK adult University Hospital ICU. 344 patients were admitted during the study period, of these 43 (12.5%) were determined to have ARDS. Patients with ARDS had increased mortality at 28 days and 2 years post-diagnosis, and there was under-recognition of ARDS in both medical records and death certificattion. Our findings have implications for critical care resource planning.

The evolving role of MDCT in the assessment of patients with chronic obstructive pulmonary disease

The purpose of this article is to educate the reader in the value a radiologist can offer in the multidetector (MD) CT assessment of patients with chronic obstructive pulmonary disease (COPD). MDCT can identify patients in whom treatments such as lung volume reduction surgery or newer endobronchial therapies may be of benefit. We will also discuss important and under-recognised associated cardiorespiratory disease, which may be incidentally identified.

S121 Assessment of interlobarcollateral ventilation prior to endobronchial valves treatment for severe emphysema

Bronchoscopic lung volume reduction (BVLR) with one-way endobronchial valves are employed to reduce hyperinflation to improve symptoms and lung function. The clinical benefits of Zephyr (PulmonX) valves in achieving target lobe volume reduction are most marked in those without collateral ventilation (CV) between ipsilateral non-target and target lobes. The presence of CV can be assessed by visual assessment of fissure integrity on CT scan and by measurement of flow and resistance following balloon catheter occlusion of the target lobe bronchus (Chartis; PulmonX). We have compared these two techniques for assessing collateral ventilation in patients with severe emphysema referred for EBV treatment. Two respiratory radiologists reviewed the CT images in 19 consecutive patients. Fissure integrity was classified as complete, incomplete minor defect, incomplete major defect. Chartis assessment for CV status was performed on potential target lobes in the same patients, and results compared for the two methods. There was 57.9% (11/19), 63.2% (12/19) and 78.9% (15/19) agreement between radiologists on fissure analysis of the right horizontal (RH), right oblique (RO) and left oblique (LO) fissures (Table 1). In 11 patients with no collateral ventilation on Chartis evaluation to the target lobe; Radiologist 1 reported 9 complete and 2 with incomplete minor defects compared to Radiologist 2; 10 complete and one with incomplete major defect. In 8 found to be CV positive by Chartis, radiologist 1; 3 complete, 3 incomplete major and 2 incomplete minor defects, and radiologist 2; 4 complete, 2 incomplete major and 2 incomplete minor defects. In conclusion, there was inter-observer difference in reporting fissure integrity particularly for right sided fissures, with better agreement for left oblique fissure. However, when experienced chest radiologists scored fissures as complete, there was a high correlation with CV negative status by Chartis. If radiologists scored fissures as incomplete major only one case was found to be CV negative whilst 2 CV negative cases were incomplete minor. This data indicates that visual assessment of fissure integrity by experienced respiratory radiologists can be used as a screening tool to determine appropriateness for subsequent Chartis EBV assessment. Abstract S121 Figure 1.

Fat Embolism Syndrome with Purtscher’s Retinopathy

A 25-year-old man was admitted after a collapse at home. He had sustained a closed tibial fracture 2 days previously while playing rugby, and was treated with a back-slab in Accident and Emergency that afternoon. On returning home, he noticed worsening blurred vision and shortness of breath. The following morning, he was found unconscious in his bed, and was brought in by ambulance to the hospital. On admission he was postictal, pyrexial (38.28C), tachypneic (26 breaths/min), and hypoxemic (PaO2 57.1 mm Hg breathing air) with a Glasgow Coma Score of 10/15. The only past history was a basal skull fracture sustained as a child. His head computed tomography (CT) scan was normal, but the CT chest showed extensive bibasal and posterior bronchovascular consolidation consistent with acute lung injury (Figure 1A). Although there was no suggestion of aspiration clinically or on CT, he was treated with intravenous antibiotics in addition to oxygen. Although his conscious level and breathlessness resolved rapidly, he then complained of visual blurring and myodesopsia, which persisted. Fundoscopy revealed bilateral cotton wool spots (Figure 1B, arrows) at the posterior poles with macular edema and multiple hemorrhages. A diagnosis of fat embolism syndrome with Purtscher’s retinopathy was made. He was treated conservatively and although he made a good recovery from a respiratory perspective, he continues to have blurred vision with an acuity of 6/24 in both eyes at 6 months.