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Pulmonary alveolar microlithiasis and probe-based confocal laser endomicroscopy.
Yserbyt, J, Alamé, T, Dooms, C, Ninane, V
Journal of bronchology & interventional pulmonology. 2013;(2):159-63
Abstract
Pulmonary alveolar microlithiasis (PAM) is a rare disease in which calcium-phosphate microliths accumulate within the alveolar space. We report cases of 2 siblings with PAM, presenting differently as regards the distribution and clinical severity. Immune cytologic analysis of bronchoalveolar lavage showed a CD4 alveolitis in the radiologically most affected patient, whereas the least affected had a normal bronchoalveolar lavage analysis, demonstrating the low specificity of immune cytologic lavage analysis in diagnosing familial PAM. For the first time, we describe the endoscopic findings using a probe-based confocal laser endomicroscopy.
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Basic science of the innate immune system and the lung.
Chaudhuri, N, Sabroe, I
Paediatric respiratory reviews. 2008;(4):236-42
Abstract
Infections of the lung are prevented first by denial of access, mediated by humoral and cellular systems that obscure the pathogen's target, simultaneously acting to kill and clear the pathogen. Where pathogens penetrate these initial defence systems, rapid detection of their presence is achieved by their engagement with a large family of pattern recognition receptors, including Toll-like receptors, retinoic-acid-inducible gene-like helicases and Nod-like receptors. Activation of a coordinated inflammatory response is achieved by cooperative signalling between sentinel leucocytes such as alveolar macrophages and lung tissue, following which a profound pro-inflammatory response mobilizes phagocytes such as neutrophils and monocytes to the lung. Resolution of the innate immune response, largely dependent upon neutrophil apoptosis, results in restoration of normal tissue architecture. In chronic disease, dysregulated inflammation maintains these systems in a state of constant activation, potentially resulting in tissue damage and progressive disease.
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Cathelicidin LL-37: LPS-neutralizing, pleiotropic peptide.
Golec, M
Annals of agricultural and environmental medicine : AAEM. 2007;(1):1-4
Abstract
Human organism, constantly exposed to a large variety of pathogenic microorganisms and their products, such as lipopolysaccharide (LPS), developed innate immunity as a first line of defence. One of the compartments of our organism well equipped with these defence mechanisms is the respiratory system. The cells lining the airways respond to the presence of virulent microorganisms by producing natural antimicrobial peptides, including the only member of the cathelicidins family found to date in humans, peptide LL-37. LL-37 is a small peptide of 37 amino acid residues. The peptide, in addition to its bactericidal effect, plays numerous roles in inflammatory and tissue remodelling processes. It stimulates angiogenesis, induces proliferation of lung epithelial cells, accelerates wound closure of the airway epithelium, and provokes cytokine release (e.g. IL-8) and cell migration. LL-37 is also able to neutralize LPS, a heteropolymer associated with organic dust, produced by Gram-negative bacteria. LPS (commonly referred to as endotoxin) plays an important role in pathogenesis of many respiratory diseases caused by organic dust, including organic dust toxic syndrome and chronic illnesses such as chronic obstructive pulmonary disease (COPD), asthma or allergic alveolitis (hypersensitivity pneumonitis). LPS is a strong pro-inflammatory stimulus, inducing in respiratory airways expression of antimicrobial peptides, including LL-37, which is in turn a potent LPS-neutralizing factor. The article discusses the complex interplay between endotoxin and the LPS-neutralizing, pleiotropic peptide LL-37 in pathogenic mechanisms of lung diseases, with regard to closer perspectives of using LL-37 and its derivatives as therapeutic agents.
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4.
Potential therapeutic role for statins in respiratory disease.
Hothersall, E, McSharry, C, Thomson, NC
Thorax. 2006;(8):729-34
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Abstract
Statins reduce cholesterol levels by inhibiting 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and have an established role in the treatment of atherosclerotic disease. Recent research has identified anti-inflammatory properties of statins. Statins appear to reduce the stability of lipid raft formation with subsequent effects on immune activation and regulation, and also prevent the prenylation of signalling molecules with subsequent downregulation of gene expression. Both these effects result in reduced cytokine, chemokine, and adhesion molecule expression, with effects on cell apoptosis or proliferation. This review considers the evidence for the anti-inflammatory properties of statins in the lung, and how these effects are being applied to research into the role of statins as a novel treatment of respiratory diseases.
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The potential of recombinant surfactant protein D therapy to reduce inflammation in neonatal chronic lung disease, cystic fibrosis, and emphysema.
Clark, H, Reid, K
Archives of disease in childhood. 2003;(11):981-4
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Abstract
By lowering surface tension at the air-water interface in the surfactant deficient premature lung, exogenous surfactant replacement therapy for neonatal respiratory distress syndrome has been highly successful in decreasing mortality after preterm birth. It has emerged in recent years that surfactant components not present in current surfactant formulations--particularly surfactant associated proteins A and D (SP-A and SP-D)-have additional roles in host defence distinct from the surface tension lowering effects of surfactant. SP-A and SP-D are calcium dependent carbohydrate binding proteins of the innate immune system important in the first line defence of the lung against microorganisms and in the control of lung inflammation. This review addresses the possibility that recently developed recombinant forms of SP-D could be useful therapeutically in attenuating inflammatory processes in neonatal chronic lung disease, cystic fibrosis, and emphysema.
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Obstructive sleep apnea.
Qureshi, A, Ballard, RD
The Journal of allergy and clinical immunology. 2003;(4):643-51; quiz 652
Abstract
Obstructive sleep apnea is an increasingly well-recognized disease characterized by periodic collapse of the upper airway during sleep. This leads to either complete or partial obstruction of the airway, resulting in apneas, hypopneas, or both. This disorder causes daytime somnolence, neurocognitive defects, and depression. It affects almost every system in the body, resulting in an increased incidence of hypertension, cardiovascular disease, stroke, pulmonary hypertension, cardiac arrhythmias, and altered immune function. It also increases the risk of having an accident, presumably as a result of associated somnolence. The gold standard for the diagnosis of sleep apnea is an overnight polysomnogram. Split-night studies are becoming increasingly common and allow for quicker implementation of therapy at a reduced cost. Treatment options for sleep apnea include weight loss, positional therapy, oral devices, continuous positive airway pressure (CPAP), and upper airway surgery. CPAP is the most efficacious and widely used therapy. Its complications include nasal congestion or dryness, mask discomfort, and claustrophobia. Heated humidifiers, newer types of masks, and nasal steroids have improved tolerance of this therapy. Bilevel positive-pressure therapy can be considered for patients who find it difficult to exhale against the consistently increased pressure of CPAP. The disease requires aggressive treatment to improve quality of life and prevent its complications.
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Gallium and other agents in diseases of the lung.
Schuster, DM, Alazraki, N
Seminars in nuclear medicine. 2002;(3):193-211
Abstract
The use of gallium for pulmonary diseases is hampered by its relative lack of specificity, typical 1- to 3-day delay between injection and imaging time, and suboptimal imaging characteristics. Other nuclear and nonnuclear imaging modalities, such as (18)F-fluorodeoxyglucose positron emission tomography (PET) and high-resolution chest computed tomography, have replaced gallium in many clinical algorithms. Yet gallium and other radiotracers, such as thallium, sestamibi, and labeled white blood cells, are useful in many specific clinical situations involving lymphoma and other neoplasias, inflammatory processes such as sarcoid and interstitial pneumonia, tuberculosis and other infections, and the acquired immune deficiency syndrome. Gallium and some of the other single-photon agents still have value in establishing a diagnosis, assessing the location and extent of disease, differentiating active disease from chronic scarring, guiding potential biopsy, and determining recurrence and response to therapy in patients with certain lung diseases, particularly when access to PET imaging is not available.
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Oxidative stress and regulation of glutathione in lung inflammation.
Rahman, I, MacNee, W
The European respiratory journal. 2000;(3):534-54
Abstract
Inflammatory lung diseases are characterized by chronic inflammation and oxidant/antioxidant imbalance, a major cause of cell damage. The development of an oxidant/antioxidant imbalance in lung inflammation may activate redox-sensitive transcription factors such as nuclear factor-KB, and activator protein-1 (AP-1), which regulate the genes for pro-inflammatory mediators and protective antioxidant genes. Glutathione (GSH), a ubiquitous tripeptide thiol, is a vital intra- and extracellular protective antioxidant against oxidative/nitrosative stresses, which plays a key role in the control of pro-inflammatory processes in the lungs. Recent findings have suggested that GSH is important in immune modulation, remodelling of the extracellular matrix, apoptosis and mitochondrial respiration. The rate-limiting enzyme in GSH synthesis is gamma-glutamylcysteine synthetase (gamma-GCS). The human gamma-GCS heavy and light subunits are regulated by AP-1 and antioxidant response elements and are modulated by oxidants, phenolic antioxidants, growth factors, and inflammatory and anti-inflammatory agents in lung cells. Alterations in alveolar and lung GSH metabolism are widely recognized as a central feature of many inflammatory lung diseases such as idiopathic pulmonary fibrosis, acute respiratory distress syndrome, cystic fibrosis and asthma. The imbalance and/or genetic variation in antioxidant gamma-GCS and pro-inflammatory versus antioxidant genes in response to oxidative stress and inflammation in some individuals may render them more susceptible to lung inflammation. Knowledge of the mechanisms of GSH regulation and balance between the release and expression of pro- and anti-inflammatory mediators could lead to the development of novel therapies based on the pharmacological manipulation of the production as well as gene transfer of this important antioxidant in lung inflammation and injury. This review describes the redox control and involvement of nuclear factor-kappaB and activator protein-1 in the regulation of cellular glutathione and gamma-glutamylcysteine synthetase under conditions of oxidative stress and inflammation, the role of glutathione in oxidant-mediated susceptibility/tolerance, gamma-glutamylcysteine synthetase genetic susceptibility and the potential therapeutic role of glutathione and its precursors in protecting against lung oxidant stress, inflammation and injury.