Immune activation in α1-antitrypsin-deficiency emphysema. Beyond the protease-antiprotease paradigm.

RATIONALE: α1-Antitrypsin (AAT) is a potent protease inhibitor, deficiency of which is associated with the presence of emphysema. An imbalance of elastase and antielastase, along with innate inflammation in the lung, is believed to cause lung destruction in α1-antitrypsin deficiency (AATD). It is now apparent that AAT has important immune-regulatory roles that would be lost in AATD, yet adaptive immune responses in the lung have not been investigated in patients with AATD. OBJECTIVES: To assess the adaptive immune response in severe AATD emphysema and compare it with that present in "usual" chronic obstructive pulmonary disease (COPD). METHODS: The immune inflammatory response in explanted lungs from 10 subjects with AATD was characterized and quantified, and the results were compared with those of 26 subjects with usual COPD and those of 17 smoking and 11 nonsmoking control subjects with normal lung function. MEASUREMENTS AND MAIN RESULTS: Lymphoid follicles (LFs) in AATD and usual COPD were markedly increased when compared with control groups. Molecular analysis of B lymphocytes in LFs showed predominantly mono/oligoclonality. LF number correlated negatively with FEV1/FVC. B lymphocytes and CD4(+) and CD8(+) T lymphocytes were significantly increased in AATD and usual COPD when compared with control groups. IL-32, an important cytokine in induction of autoimmunity, was markedly up-regulated in AATD and usual COPD. CONCLUSIONS: An important adaptive immune inflammation, comprising B, CD4(+), and CD8(+) lymphocytes, and LFs, is a prominent feature in AATD. These results change the paradigm of the mechanism of AATD-induced emphysema from a pure elastase-antielastase imbalance to a much more complex one involving the adaptive immune system, similarly to what occurs in usual COPD.

Right-to-left interatrial shunt secondary to right hemidiaphragmatic paralysis: an unusual scenario for urgent percutaneous closure of patent foramen ovale.

A 66 year-old female presented with a refractory hypoxaemia in association with an isolated paralysis of the right hemidiaphragm. Transoesophageal echocardiography (TEE) with both colour Doppler and bubble test demonstrated a significant patent foramen ovale (PFO)-mediated right-to-left shunt (RTLS) without an increased interatrial pressure gradient. The PFO was urgently closed by deployment of an AMPLATZER(®) occluder device, resulting in complete recovery of the arterial oxygen saturation and patient's symptoms. As noted on TEE, the RTLS was due to redirection of blood flow from the inferior vena cava directly through the PFO secondary to distortion of the cardiac anatomy by right hemidiaphragmatic paralysis.

Is chronic obstructive pulmonary disease a disease of aging?

Chronic obstructive pulmonary disease (COPD) is a disease that usually presents clinically at an advanced age, after years of smoking cigarettes. It is usually believed that aging and its biological consequences are important mechanisms in the disease pathogenesis. This concept has maintained the focus of studies on COPD in old-age individuals. Here we analyze the possible role of aging from a different point of view and introduce different concepts that might be considered useful additions to the understanding of the disease. Essentially, we propose and show evidence that COPD is a disease of the young susceptible smoker that progresses over time and manifests in older age because we live longer and not so much because of the effect of aging itself; we examine the concept of cell senescence, the basis of tissue aging, and how stressors like the ones produced by smoking can accelerate cell senescence with all of its untoward consequences in COPD. We thus finally suggest that COPD might accelerate aging rather than be a consequence of it. In conclusion, we suggest that COPD could be considered a disease of the predisposed young individual that manifests clinically in old age because we live longer, with all of its consequences.

Primary Pulmonary Epithelioid Hemangioendothelioma: A Rare Cause of PET-Negative Pulmonary Nodules.

We report here a case of primary pulmonary epithelioid hemangioendothelioma diagnosed in a 67-year-old Caucasian man, presenting with exertion dyspnoea, dry cough, and multiple bilateral pulmonary nodules revealed by computed tomography. At the 18F-fluorodeoxyglucose positron emission tomography, these nodules were negative. The histopathological diagnosis was made on a pulmonary wedge resection (performed during video-thoracoscopic surgery).