Natural history of chronic thromboembolic pulmonary disease with no or mild pulmonary hypertension.

BACKGROUND: We describe baseline characteristics, disease progression and mortality in chronic thromboembolic pulmonary disease patients as a function of mean pulmonary artery pressure (mPAP) according to new and previous definitions of pulmonary hypertension. METHODS: All patients diagnosed with chronic thromboembolic pulmonary disease between January, 2015 and December, 2019 were dichotomized according to initial mPAP: ≤ 20 mmHg ('normal') vs 21-24 mmHg ('mildly-elevated'). Baseline features were compared between the groups, and pairwise analysis performed to determine changes in clinical endpoints at 1-year, excluding those who underwent pulmonary endarterectomy or did not attend follow-up. Mortality was assessed for the whole cohort over the entire study period. RESULTS: One hundred thirteen patients were included; 57 had mPAP ≤ 20 mmHg and 56 had mPAP 21-24 mmHg. Normal mPAP patients had lower pulmonary vascular resistance (1.6 vs 2.5WU, p < 0.01) and right ventricular end-diastolic pressure (5.9 vs 7.8 mmHg, p < 0.01) at presentation. At 3 years, no major deterioration was seen in either group. No patients were treated with pulmonary artery vasodilators. Eight had undergone pulmonary endarterectomy. Over 37 months median follow-up, mortality was 7.0% in the normal mPAP group and 8.9% in the mildly-elevated mPAP group. Cause of death was malignancy in 62.5% of cases. CONCLUSIONS: Chronic thromboembolic pulmonary disease patients with mild pulmonary hypertension have statistically higher right ventricular end-diastolic pressure and pulmonary vascular resistance than those with mPAP ≤ 20 mmHg. Baseline characteristics were otherwise similar. Neither group displayed disease progression on non-invasive tests up to 3 years. Mortality over 37 months follow-up is 8%, and mainly attributable to malignancy. Further prospective study is required to validate these findings.

Treatment of COVID-19 with remdesivir in the absence of humoral immunity: a case report.

The response to the coronavirus disease 2019 (COVID-19) pandemic has been hampered by lack of an effective severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antiviral therapy. Here we report the use of remdesivir in a patient with COVID-19 and the prototypic genetic antibody deficiency X-linked agammaglobulinaemia (XLA). Despite evidence of complement activation and a robust T cell response, the patient developed persistent SARS-CoV-2 pneumonitis, without progressing to multi-organ involvement. This unusual clinical course is consistent with a contribution of antibodies to both viral clearance and progression to severe disease. In the absence of these confounders, we take an experimental medicine approach to examine the in vivo utility of remdesivir. Over two independent courses of treatment, we observe a temporally correlated clinical and virological response, leading to clinical resolution and viral clearance, with no evidence of acquired drug resistance. We therefore provide evidence for the antiviral efficacy of remdesivir in vivo, and its potential benefit in selected patients.

Correction to: Imaging of Bronchial Pathology in Antibody Deficiency: Data from the European Chest CT Group.

In the original version of this article unfortunately two authors were missing: Dr. Jürgen Weidemann and Dr. Daniel Berthold. The correct list of authors is presented above.

Implementing lung cancer screening: baseline results from a community-based 'Lung Health Check' pilot in deprived areas of Manchester.

We report baseline results of a community-based, targeted, low-dose CT (LDCT) lung cancer screening pilot in deprived areas of Manchester. Ever smokers, aged 55-74 years, were invited to 'lung health checks' (LHCs) next to local shopping centres, with immediate access to LDCT for those at high risk (6-year risk ≥1.51%, PLCOM2012 calculator). 75% of attendees (n=1893/2541) were ranked in the lowest deprivation quintile; 56% were high risk and of 1384 individuals screened, 3% (95% CI 2.3% to 4.1%) had lung cancer (80% early stage) of whom 65% had surgical resection. Taking lung cancer screening into communities, with an LHC approach, is effective and engages populations in deprived areas.

Second round results from the Manchester 'Lung Health Check' community-based targeted lung cancer screening pilot.

We report results from the second annual screening round (T1) of Manchester's 'Lung Health Check' pilot of community-based lung cancer screening in deprived areas (undertaken June to August 2017). Screening adherence was 90% (n=1194/1323): 92% of CT scans were classified negative, 6% indeterminate and 2.5% positive; there were no interval cancers. Lung cancer incidence was 1.6% (n=19), 79% stage I, treatments included surgery (42%, n=9), stereotactic ablative radiotherapy (26%, n=5) and radical radiotherapy (5%, n=1). False-positive rate was 34.5% (n=10/29), representing 0.8% of T1 participants (n=10/1194). Targeted community-based lung cancer screening promotes high screening adherence and detects high rates of early stage lung cancer.

Imaging of Bronchial Pathology in Antibody Deficiency: Data from the European Chest CT Group.

Studies of chest computed tomography (CT) in patients with primary antibody deficiency syndromes (ADS) suggest a broad range of bronchial pathology. However, there are as yet no multicentre studies to assess the variety of bronchial pathology in this patient group. One of the underlying reasons is the lack of a consensus methodology, a prerequisite to jointly document chest CT findings. We aimed to establish an international platform for the evaluation of bronchial pathology as assessed by chest CT and to describe the range of bronchial pathologies in patients with antibody deficiency. Ffteen immunodeficiency centres from 9 countries evaluated chest CT scans of patients with ADS using a predefined list of potential findings including an extent score for bronchiectasis. Data of 282 patients with ADS were collected. Patients with common variable immunodeficiency disorders (CVID) comprised the largest subgroup (232 patients, 82.3%). Eighty percent of CVID patients had radiological evidence of bronchial pathology including bronchiectasis in 61%, bronchial wall thickening in 44% and mucus plugging in 29%. Bronchiectasis was detected in 44% of CVID patients aged less than 20 years. Cough was a better predictor for bronchiectasis than spirometry values. Delay of diagnosis as well as duration of disease correlated positively with presence of bronchiectasis. The use of consensus diagnostic criteria and a pre-defined list of bronchial pathologies allows for comparison of chest CT data in multicentre studies. Our data suggest a high prevalence of bronchial pathology in CVID due to late diagnosis or duration of disease.

The outcome of reoperative pulmonary endarterectomy surgery.

OBJECTIVES: Pulmonary endarterectomy (PEA) is the treatment of choice for patients with chronic thromboembolic pulmonary hypertension (PH). Despite excellent outcomes following PEA, a small proportion of patients have residual proximal disease or present with recurrent chronic thromboembolic PH and may benefit from further surgery. The aim of this study was to analyse outcomes following reoperative PEA at a high-volume national tertiary referral centre for the management of chronic thromboembolic PH. METHODS: This retrospective analysis was performed using our prospectively maintained PH database to identify all patients who underwent reoperative PEA surgery between the commencement of the programme in 1997 and January 2017, and the patients' data were collected for analysis. RESULTS: Twelve patients underwent reoperative PEA during the period of study. The mean interval between primary procedure and reoperative procedure was 6.3 years. Significant improvements were observed in pulmonary haemodynamics following reoperative PEA. Mean pulmonary arterial pressure decreased from 46.8 to 29.8 mmHg (P < 0.0001) and pulmonary vascular resistance decreased from 662 to 362 dyne·s·cm-5 (P = 0.0007). A significant functional improvement in the 6-min walking test distance was also observed, increasing from 327 to 460 m at 6 months postoperatively (P = 0.0018). Median length of hospital stay was 12 days. In-hospital mortality was 8.3% with 1-year survival of 83.3%. CONCLUSIONS: Reoperative PEA is technically possible and relatively safe, achieving good functional and physiological outcomes. Patients must be carefully selected by a multidisciplinary team, and surgery should be performed in experienced centres.

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

BACKGROUND: Activated phosphoinositide 3-kinase δ 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 δ (PI3Kδ). 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 PI3Kδ in the central nervous system; consistent with this, PI3Kδ 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 PI3Kδ inhibitors offer new prospects for APDS treatment.

Improving care for patients with idiopathic pulmonary fibrosis (IPF) in the UK: a round table discussion.

This article is the result of a round table discussion held at BMA House. Its purpose is to outline the challenges facing both patients and doctors in managing idiopathic pulmonary fibrosis. A number of recommendations for service development and research have been identified.

Right ventricular reverse remodeling after pulmonary endarterectomy: magnetic resonance imaging and clinical and right heart catheterization assessment.

The objective of this study was to assess the effect of pulmonary endarterectomy (PEA) on right ventricular (RV) reverse remodeling using magnetic resonance imaging (MRI) and to correlate MRI findings with clinical and hemodynamic outcomes postsurgery. We performed a retrospective analysis in 72 patients undergoing PEA surgery in whom MRI and right heart catheterization (RHC) were performed preoperation and 3 months postoperation. RV volumes and mass were assessed by MRI. Continuous variables were expressed as means, changes were compared with a paired t test, and associations between the variables were explored using Pearson correlation coefficients. The mean age was 57 years, and 51% were male. Both RV end-diastolic volume (EDV; 176-117 mL; P < 0.001) and RV end-systolic volume (ESV; 129-64 mL; P < 0.001) reduced significantly following PEA. Preoperative pulmonary artery pressure (PAP) correlated moderately with ESV (r = 0.46, P < 0.001). Postoperatively, PAP correlated with EDV (r = 0.45, P < 0.001) and ESV (r = 0.44, P < 0.001). Moderate correlation was present between hemodynamic parameters: PAP, pulmonary vascular resistance, and right atrial pressure with pre- and postoperation end-systolic and end-diastolic RV mass (P < 0.001). RHC and MRI measurements of cardiac output and RV volumes were significantly different (P < 0.001). In conclusion, RV reverse remodeling, as measured by improvement in RV volumes and mass by MRI, was observed for 3 months in patients who underwent PEA surgery. This is the largest series of patients with pre- and post-PEA MRI assessment so far reported. MRI detects changes in parameters reflecting cardiac remodeling and pulmonary clearance, but measurements are significantly different from those of RHC.

The importance of correction for tissue fraction effects in lung PET: preliminary findings.

PURPOSE: It has recently been recognized that PET/CT may play a role in diffuse parenchymal lung disease. However, interpretation can be confounded due to the variability in lung density both within and between individuals. To address this issue a novel correction method is proposed. METHODS: A CT scan acquired during shallow breathing is registered to a PET study and smoothed so as to match the PET resolution. This is used to derive voxel-based tissue fraction correction factors for the individual. The method was evaluated in a lung phantom study in which the lung was simulated by a Styrofoam/water mixture. The method was further evaluated using (18)F-FDG in 12 subjects free from pulmonary disease where ranges before and after correction were considered. RESULTS: Correction resulted in similar activity concentrations for the lung and background regions, consistent with the experimental phantom set-up. Correction resulted in reduced inter- and intrasubject variability in the estimated SUV. The possible application of the method was further demonstrated in five subjects with interstitial lung changes where increased SUV was demonstrated. Single study pre- and post-treatment studies were also analysed to further illustrate the utility of the method. CONCLUSION: The proposed tissue fraction correction method is a promising technique to account for variability of density in interpreting lung PET studies.

The cardiothoracic ratio--an inaccurate and outdated measurement: new data from CT.

Cardiomegaly (and left ventricular size in particular) is well recognized to have cardiovascular prognostic significance. Cardiac assessment should be routinely performed when evaluating imaging studies encompassing the thorax, whether cross sectional or projectional. However, such measurements should be robust, readily available and practical. In this issue of European Radiology, Schlett et al. describe such a technique based on single level area and transverse diameter measurements on transverse CT and projection digitally acquired radiographs. This paper is significant as it makes a simple tool for left ventricular assessment readily available to all cross-sectional imagers and highlights the established limitation of cardiothoracic ratio on the chest radiograph.