Alpha1-antitrypsin deficiency: An updated review.

Alpha1-antitrypsin deficiency (AATD) is a rare autosomal recessive disease associated with the homozygous Z variant of the SERPINA1 gene. Clinical expression of AATD, reported 60 years ago associate a severe deficiency, pulmonary emphysema and/or liver fibrosis. Pulmonary emphysema is due to the severe alpha1-antitrypsin deficiency of the ZZ homozygous status and is favored by smoking. Liver fibrosis is due to the ZZ homozygous status and is favored by obesity and excessive chronic alcohol intake, with a risk of liver cancer. Diagnosis is based on serum level and either isoelectric focusing determination of the biochemical phenotype or PCR detection of some variants. SERPINA1 gene sequencing is necessary in case of discrepancies between the results of these tests. No treatment is available for the liver disease in AATD. Although no specific trial has been performed, COPD in AATD should be treated as per COPD recommendations. Based on a randomized clinical trial, augmentation therapy is indicated in non-smoking adults less than 70 years of age with emphysema at chest CT, confirmed homozygous AATD, and FEV1 between 35% and 70% of predicted. In contrast Z heterozygosis (MZ or SZ) brings a risk of lung or liver disease only in association with further risk factors. Early detection, in all patients with COPD and chronic liver disease, is critical for the correct information of Z variant carriers. News ways of correcting the liver production of alpha1-antitrypsin will modify the care of AATD patients.

Effect of contrast material injection protocol on first-pass myocardial perfusion assessed by dual-energy dual-layer computed tomography.

Background: Dual-energy dual-layer computed tomography (CT) scanners can provide useful tools, such as iodine maps and virtual monochromatic images (VMI), for the evaluation of myocardial perfusion defects. Data about the influence of acquisition protocols and normal values are still lacking. Methods: Clinically indicated coronary CT-angiographies performed between January-October 2018 in a single university hospital with dual-energy dual-layer CT (DE-DLCT) and different injection protocols were retrospectively evaluated. The two protocols were: 35 mL in patients <80 kg and 0.5 mL/kg in patients >80 kg at 2.5 mL/s (group A) or double contrast dose at 5 mL/s (group B). Patients with coronary stenosis >50% were excluded. Regions of interest were manually drawn on 16 myocardial segments and iodine concentration was measured in mg/mL. Signal-to-noise, contrast-to-noise ratios (CNR) and image noise were measured on conventional images and VMI. Results: A total of 30 patients were included for each protocol. With iodine concentrations of 1.38±0.41 mg/mL for protocol A and 2.07±0.73 mg/mL for protocol B, the two groups were significantly different (P<0.001). No significant iodine concentration differences were found between the 16 segments (P=0.47 and P=0.09 for group A and B respectively), between basal, mid and apical segments for group A and B (P=0.28 and P=0.12 for group A and B respectively) and between wall regions for group A (P=0.06 on normalised data). In group B, iodine concentration was significantly different between three wall regions [highest values for the lateral wall, median =2.03 (1.06) mg/mL]. Post-hoc analysis showed highest contrast-to-noise and signal-to-noise in VMI at 40 eV (P<0.05). Conclusions: Iodine concentration in left ventricular myocardium of patients without significant coronary artery stenosis varied depending on the injection protocol and appeared more heterogeneous in different wall regions at faster injection rate and greater iodine load. Signal-to-noise and contrast-to-noise gradually improved when decreasing VMI energy, although at the expenses of higher noise, demonstrating the potential of DE-DLCT to enhance objective image quality.

Embolization of Recurrent Pulmonary Arteriovenous Malformations by Ethylene Vinyl Alcohol Copolymer (Onyx®) in Hereditary Hemorrhagic Telangiectasia: Safety and Efficacy.

OBJECTIVES: To evaluate short- and long-term safety and efficacy of embolization with Onyx® for recurrent pulmonary arteriovenous malformations (PAVMs) in hereditary hemorrhagic telangiectasia (HHT). METHODS: In total, 45 consecutive patients (51% women, mean (SD) age 53 (18) years) with HHT referred to a reference center for treatment of recurrent PAVM were retrospectively included from April 2014 to July 2021. Inclusion criteria included evidence of PAVM recurrence on CT or angiography, embolization using Onyx® and a minimal 1-year-follow-up CT or angiography. Success was defined based on the standard of reference criteria on unenhanced CT or pulmonary angiography if a recurrence was suspected. PAVMs were analyzed in consensus by two radiologists. The absence of safety distance, as defined by a too-short distance for coil/plug deployment, i.e., between 0.5 and 1 cm, between the proximal extremity of the primary embolic material used and a healthy upstream artery branch, was reported. RESULTS: In total, 70 PAVM were analyzed. Mean (SD) follow-up was 3 (1.3) years. Safety distance criteria were missing in 33 (47%) PAVMs. All procedures were technically successful, with a short-term occlusion rate of 100% using a mean (SD) of 0.6 (0.5) mL of Onyx®. The long-term occlusion rate was 60%. No immediate complication directly related to embolization was reported, nor was any severe long-term complication such as strokes or cerebral abscesses. CONCLUSIONS: In HHT, treatment of recurrent PAVM with Onyx® showed satisfactory safety and efficacy, with an immediate occlusion rate of 100% and a long-term rate of 60%.

Progressive fibrosing interstitial lung disease: a clinical cohort (the PROGRESS study).

In patients with chronic fibrosing interstitial lung disease (ILD), a progressive fibrosing phenotype (PF-ILD) may develop, but information on the frequency and characteristics of this population outside clinical trials is lacking.We assessed the characteristics and outcomes of patients with PF-ILD other than idiopathic pulmonary fibrosis (IPF) in a real-world, single-centre clinical cohort. The files of all consecutive adult patients with fibrosing ILD (2010-2017) were examined retrospectively for pre-defined criteria of ≥10% fibrosis on high-resolution computed tomography and progressive disease during overlapping windows of 2 years. Baseline was defined as the date disease progression was identified. Patients receiving nintedanib or pirfenidone were censored from survival and progression analyses.In total, 1395 patients were screened; 617 had ILD other than IPF or combined pulmonary fibrosis and emphysema, and 168 had progressive fibrosing phenotypes. In 165 evaluable patients, median age was 61 years; 57% were female. Baseline mean forced vital capacity (FVC) was 74±22% predicted. Median duration of follow-up was 46.2 months. Annualised FVC decline during the first year was estimated at 136±328 mL using a linear mixed model. Overall survival was 83% at 3 years and 72% at 5 years. Using multivariate Cox regression analysis, mortality was significantly associated with relative FVC decline ≥10% in the previous 24 months (p<0.05), age ≥50 years (p<0.01) and diagnosis subgroup (p<0.01).In this cohort of patients with PF-ILD not receiving antifibrotic therapy, the disease followed a course characterised by continued decline in lung function, which predicted mortality.

Comparative assessment of image quality for coronary CT angiography with iobitridol and two contrast agents with higher iodine concentrations: iopromide and iomeprol. A multicentre randomized double-blind trial.

OBJECTIVES: To demonstrate non-inferiority of iobitridol 350 for coronary CT angiography (CTA) compared to higher iodine content contrast media regarding rate of patients evaluable for the presence of coronary artery stenoses. METHODS: In this multicentre trial, 452 patients were randomized to receive iobitridol 350, iopromide 370 or iomeprol 400 and underwent coronary CTA using CT systems with 64-detector rows or more. Two core lab readers assessed 18 coronary segments per patient regarding image quality (score 0 = non diagnostic to 4 = excellent quality), vascular attenuation, signal and contrast to noise ratio (SNR, CNR). Patients were considered evaluable if no segment had a score of 0. RESULTS: Per-patient, the rate of fully evaluable CT scans was 92.1, 95.4 and 94.6 % for iobitridol, iopromide and iomeprol, respectively. Non-inferiority of iobitridol over the best comparator was demonstrated with a 95 % CI of the difference of [-8.8 to 2.1], with a pre-specified non-inferiority margin of -10 %. Although average attenuation increased with higher iodine concentrations, average SNR and CNR did not differ between groups. CONCLUSIONS: With current CT technology, iobitridol 350 mg iodine/ml is not inferior to contrast media with higher iodine concentrations in terms of image quality for coronary stenosis assessment. KEY POINTS: • Iodine concentration is an important parameter for image quality in coronary CTA. • Contrast enhancement must be balanced against the amount of iodine injected. • Iobitridol 350 is non-inferior compared to CM with higher iodine concentrations. • Higher attenuation with higher iodine concentrations, but no SNR or CNR differences.

Hypereosinophilic obliterative bronchiolitis: a distinct, unrecognised syndrome.

Biopsy-proven cases of eosinophilic bronchiolitis have only been reported in isolation, and all come from Japan. We present six patients with hypereosinophilic obliterative bronchiolitis (HOB), defined by the following criteria: 1) blood eosinophil cell count >1 G·L(-1) and/or bronchoalveolar lavage eosinophil count >25%; 2) persistent airflow obstruction despite high-dose inhaled bronchodilators and corticosteroids; and 3) eosinophilic bronchiolitis at lung biopsy (n=1) and/or direct signs of bronchiolitis (centrilobular nodules and branching opacities) on computed tomography (n=6). Chronic dyspnoea and cough which was often severe, without the characteristic features of asthma, were the main clinical manifestations. Atopy and asthma were present in the history of three and two patients, respectively. One patient met biological criteria of the lymphoid variant of idiopathic hypereosinophilic syndrome. Mean blood eosinophil cell count was 2.7 G·L(-1) and mean eosinophil differential percentage at bronchoalveolar lavage was 63%. Mean initial forced expiratory volume in 1 s/forced vital capacity ratio was 50%, normalising with oral corticosteroid therapy in all patients. HOB manifestations recurred when oral prednisone was decreased to 10-20 mg·day(-1), but higher doses controlled the disease. HOB is a characteristic entity deserving to be individualised among the eosinophilic respiratory disorders. Thorough analysis is needed to determine whether unrecognised and/or smouldering HOB may further be a cause of irreversible airflow obstruction in chronic eosinophilic respiratory diseases.

Combined pulmonary fibrosis and emphysema syndrome in connective tissue disease.

OBJECTIVE: Connective tissue diseases (CTDs) are associated with several interstitial lung diseases. The aim of this study was to describe the recently individualized syndrome of combined pulmonary fibrosis and emphysema (CPFE) in a population of patients with CTD. METHODS: In this multicenter study, we retrospectively investigated data from patients with CTD who also have CPFE. The demographic characteristics of the patients, the results of pulmonary function testing, high-resolution computed tomography, lung biopsy, and treatment, and the outcomes of the patients were analyzed. RESULTS: Data from 34 patients with CTD who were followed up for a mean±SD duration of 8.3±7.0 years were analyzed. Eighteen of the patients had rheumatoid arthritis (RA), 10 had systemic sclerosis (SSc), 4 had mixed or overlap CTD, and 2 had other CTDs. The mean±SD age of the patients was 57±11 years, 23 were men, and 30 were current or former smokers. High-resolution computed tomography revealed emphysema of the upper lung zones and pulmonary fibrosis of the lower zones in all patients, and all patients exhibited dyspnea during exercise. Moderately impaired pulmonary function test results and markedly reduced carbon monoxide transfer capacity were observed. Five patients with SSc exhibited pulmonary hypertension. Four patients died during followup. Patients with CTD and CPFE were significantly younger than an historical control group of patients with idiopathic CPFE and more frequently were female. In addition, patients with CTD and CPFE had higher lung volumes, lower diffusion capacity, higher pulmonary pressures, and more frequently were male than those with CTD and lung fibrosis without emphysema. CONCLUSION: CPFE warrants inclusion as a novel, distinct pulmonary manifestation within the spectrum of CTD-associated lung diseases in smokers or former smokers, especially in patients with RA or SSc.

Noninvasive assessment of the prevalence and characteristics of coronary atherosclerotic plaques by multidetector computed tomography in asymptomatic type 2 diabetic patients at high risk of significant coronary artery disease: a preliminary study.

BACKGROUND: There is a need to identify diabetic patients at risk of cardiovascular events before symptom onset. AIMS: To evaluate the prevalence and characteristics of coronary atherosclerotic plaques in asymptomatic type 2 diabetic patients with coronary risk factors but without known coronary artery disease, using multidetector computed tomography. METHODS: High-resolution 40-slice coronary computed tomography was performed prospectively in 42 consecutive type 2 diabetic patients (mean age 62 years; range 50-77 years; 28 men) with over one or more carotid atherosclerotic plaque and no coronary artery disease symptoms. Computed tomography data were evaluated for calcium score and the presence of coronary plaques. Plaque type, distribution, extensive character and obstructive nature were determined per patient for each segment. RESULTS: No plaques were detected in 11 (26.2%) patients. Atherosclerotic plaques were detected in 31 (73.8%) patients. A total of 147 coronary segments with plaque were identified, of which 11 (7.5%) contained hypodense plaques, 28 (19%) mixed plaques and 108 (73.5%) calcified plaques. Hypodense plaques were noted in 4/15 (26.7%) patients without coronary calcifications. Most calcified and hypodense plaques resulted in lumen narrowing of less than 50%; most mixed plaques resulted in lumen narrowing greater than 50%. Obstructive disease was detected in 9/11 patients with a high calcium score (>400). CONCLUSION: This preliminary study demonstrates that a high proportion of asymptomatic type 2 diabetic patients present without coronary plaques detectable by multidetector computed tomography, despite concomitant carotid atherosclerotic lesions. Computed tomography seems to detect a high proportion of plaques compared with conventional angiography in these specific patients.

Endovascular repair of lesions involving the descending thoracic aorta. Mid-term morphological changes.

Thoracic aortic lesions are often life-threatening conditions with significant morbidity and mortality after open surgical repair. If preliminary results suggest that endovascular therapy is an effective and advantageous treatment, long-term effectiveness remains questionable. We analysed 75 consecutive patients who underwent endovascular stent-grafting of lesions involving the descending thoracic aorta (32 emergent, 43 elective). Aortic pathologies were aneurysms (n=31), chronic (n=8) or complicated (n=6) type B dissections, penetrating ulcers (n=4) or aortic ruptures (n=26). Follow-up was performed using magnetic resonance angiography. In three cases, the procedure was stopped due to inappropriate arterial access calibre. The hospital mortality and morbidity were 8% and 12%, respectively. One patient of the chronic group presented a type I endoleak, treated by embolisation. After 1.5 months, the mortality and morbidity rates were 10.6% and 10.6%, respectively. The secondary endoleak rate was 16%. One patient died of aortic rupture 24 months after the procedure. In the aneurysm group, the regression of the aortic calibre was significant in 23 and stable in 28 patients. Thus, and despite encouraging early outcomes, mid-term results suggest a trend toward increased re-intervention and late complication rates in these high surgical risk patients. Therefore, continued surveillance of patients treated with stent-grafts is necessary.

Endovascular repair of localized pathological lesions of the descending thoracic aorta: midterm results.

The endoluminal stent-graft represents an attractive and a less invasive technique for treatment of various diseases of the descending thoracic aorta. The purpose of this study was to evaluate the Talent endovascular stent-graft for the treatment of various localized diseases of the descending thoracic aorta. Over a 3-year period, Talent thoracic endografts were placed in 40 patients with a high surgical risk, presenting a localized lesion of the descending thoracic aorta: degenerative aneurysm (n = 13), acute traumatic rupture (n = 11), acute Stanford type B aortic dissection (n = 6), false aneurysm (n = 7), and penetrating atherosclerotic ulcer (n = 3). Fifteen patients (37.5%) were treated as emergencies. The feasibility of endovascular treatment and sizing of the aorta and stent-grafts were determined preoperatively by magnetic resonance angiography (MRA) and intraoperative angiography. Immediate and mid-term technical and clinical success was assessed by clinical and MRA follow-up. Endovascular treatment was completed successfully in all 40 patients, with no conversion to open repair or intraoperative mortality. The mean operative time was 37.5 +/- 7 min. The overall 30-day mortality rate was 10% (n = 4), all in emergency cases, for causes not related to the endograft. The primary technical success was 92.5%. The mean follow-up period was 15 +/- 5 months. The survival rate was 95% (n = 35). Diminution of the aneurismal size was observed in 47.5% (n = 19). We conclude that endovascular treatment of the various localized diseases of the descending thoracic aorta is a promising, feasible, alternative technique to open surgery in well-selected patients.

Abdominal CT angiography before surgery as a predictor of postoperative death in acute aortic dissection.

OBJECTIVE: The purpose of our study was to search for a relationship between postoperative death in acute aortic dissection and abdominal helical CT findings before surgery. MATERIALS AND METHODS: We retrospectively included 48 patients admitted to our institution for emergent surgery of acute aortic dissection diagnosed with helical CT angiography. We recorded postoperative deaths and analyzed abdominal helical CT vessels and parenchymal abnormalities, including the presence of dissected abdominal aortic branches, a compressed aortic lumen, and low enhancement of the parenchyma in abdominal organs. RESULTS: Among the 48 patients, 11 died after surgery. Postoperative death occurred in one of five patients with low enhancement of the parenchyma in one abdominal organ and in seven of eight patients with low enhancement of the parenchyma in at least two abdominal organs. The postoperative death rates strongly correlated with the number of low-enhanced abdominal organs per patient (p < 0.00005) but did not correlate with the number of dissected abdominal aortic branches. CONCLUSION: The rate of abdominal organs with low enhancement of the parenchyma seen on CT before surgery is a strong factor in outcome in patients with acute aortic dissection. Additional analysis of low enhancement of the parenchyma in abdominal organs on CT might be a useful tool to detect, before surgery, patients at risk of postoperative death.

Pulmonary arteriovenous malformations in patients with hereditary hemorrhagic telangiectasia.

Pulmonary arteriovenous malformations (PAVMs) associated with hereditary hemorrhagic telangiectasia may cause severe cerebral complications that may be prevented by embolization therapy. We retrospectively compared the diagnostic value of noninvasive tests for the screening of treatable (amenable to embolization) PAVMs in a series of 105 patients, using chest computerized tomography (CT) and/or pulmonary angiography as a "gold standard." Patients had assessment of dyspnea, chest radiograph, alveolar-arterial PO2 gradient under 100% oxygen (AaPO2), contrast echocardiography, and radionuclide perfusion lung scanning. Contrast echocardiography in the supine position was the most sensitive test (93%). The sensitivity of self-reported dyspnea (59%), chest radiograph alone (70%), measurement of AaPO2 by the 100% oxygen method (62%), or radionuclide lung scanning (71%), was not suitable for efficient screening. A 100% sensitivity and negative predictive value could be obtained when combining anteroposterior chest radiograph and contrast echocardiography. Our data support a screening algorithm based on the combined use of contrast echocardiography and anteroposterior chest radiograph, followed by chest CT if either test is positive. An alternative is to screen directly by chest CT. However, this algorithm may obviate the need for chest CT in patients without PAVM, who represent a majority of patients with hereditary hemorrhagic telangiectasia.