Modern Pharmacotheraphy of Lung Disease: Anti-Leukotriene Agents for the Treatment of Lung Disease.

Am J Respir Crit Care Med. 2013 Jul 3;

Authors: Scott JP, Peters-Golden M

Abstract
Leukotrienes (LTs) C4, D4, and E4, collectively termed cysteinyl LTs (cysLTs), are lipid mediators formed by the 5-lipoxygenase (5-LO) pathway of arachidonic acid metabolism. Originally recognized for their potent bronchoconstrictor actions, they were subsequently determined to also promote inflammation, microvascular permeability, and mucus secretion. These actions that are so central to asthma pathophysiology are mediated to a significant extent by ligation of the cysLT receptor 1 (CysLT1). Antagonism of CysLT1 and inhibition of 5-LO have both been shown to have clinical utility in the management of asthma, but substantial inter-individual heterogeneity is observed in the response to these agents. In this article, we review the biologic actions of LTs, their biosynthetic pathways and cognate receptors, the pharmacology of available anti-LT agents, and the clinical evidence for the use of anti-LT agents as mono-therapy and combination therapy in asthma. We also consider heterogeneity of response, the possible roles of cysLT receptors other than CysLT1, the role of another class of LT, LTB4, and the potential role of LTs in lung diseases other than asthma.

PMID: 23822826 [PubMed - as supplied by publisher]

Related Articles

Diagnostic usefulness of an amino acid tracer, α-[N-methyl-(11)C]-methylaminoisobutyric acid ( (11)C-MeAIB), in the PET diagnosis of chest malignancies.

Ann Nucl Med. 2013 Jul 4;

Authors: Nishii R, Higashi T, Kagawa S, Kishibe Y, Takahashi M, Yamauchi H, Motoyama H, Kawakami K, Nakaoku T, Nohara J, Okamura M, Watanabe T, Nakatani K, Nagamachi S, Tamura S, Kawai K, Kobayashi M

Abstract
OBJECTIVES: Although positron emission tomography (PET) using [(18)F]-fluoro-2-deoxy-D-glucose ((18)F-FDG) is established as one of the first-choice imaging modalities in the diagnosis of chest malignancies, there are several problems to solve in clinical practice, such as false positive uptake in inflammatory diseases. The aim of this study was to evaluate the clinical usefulness of an amino acid tracer, α-[N-methyl-(11)C]-methylaminoisobutyric acid ((11)C-MeAIB), in the diagnosis of chest malignancies, in combination with (18)F-FDG.
SETTING: Fifty-nine cases (57 patients, 66 ± 12 years old) who consulted to our institution for the wish to receive differential diagnosis of chest diseases were included. Purpose of the studies were as follows: differential diagnosis of newly developed lung nodules, n = 22; newly developed mediastinal lesions, n = 20; and both, n = 17 (including lung cancer: n = 19, lymphoma: n = 1, other cancers: n = 2, sarcoidosis: n = 15, non-specific inflammation: n = 18, other inflammatory: n = 4, respectively). Whole-body static PET or PET/CT scan was performed 20 and 50 min after the IV injection of (11)C-MeAIB and (18)F-FDG, respectively.
RESULTS: (11)C-MeAIB uptake of malignant and benign lesions was statistically different both in pulmonary nodules (p < 0.005) and in mediastinal lesions (p < 0.0005). In visual differential diagnosis, (11)C-MeAIB showed higher results (specificity: 73 %, accuracy: 81 %), compared to those in (18)F-FDG (60, 73 %, respectively). In cases of sarcoidosis, (11)C-MeAIB showed higher specificity (80 %) with lower uptake (1.8 ± 0.7) in contrast to the lower specificity (60 %) with higher uptake of (18)F-FDG (7.3 ± 4.5).
CONCLUSIONS: (11)C-MeAIB PET/CT was useful in the differential diagnosis of pulmonary and mediastinal mass lesions found on CT. (11)C-MeAIB PET or PET/CT showed higher specificity than that of (18)F-FDG PET/CT in differentiating between benign and malignant disease. Our data suggest that the combination of (18)F-FDG and (11)C-MeAIB may improve the evaluation of chest lesions, when CT and (18)F-FDG PET/CT are equivocal.

PMID: 23824782 [PubMed - as supplied by publisher]

Related Articles

The diagnosis efficacy and safety of video-assisted thoracoscopy surgery (VATS) in undefined interstitial lung diseases: a retrospective study.

J Thorac Dis. 2013 Jun;5(3):283-8

Authors: Luo Q, Han Q, Chen X, Xie J, Wu L, Chen R

Abstract
OBJECTIVES: To evaluate the efficacy and safety of lung biopsies by video-assisted thoracoscopy surgery (VATS) in the diagnosis of undefined interstitial lung disease (ILD).
PATIENTS AND METHODS: The retrospective analysis was performed in 32 who patients underwent VATS for the diagnosed with ILD from Jan 2007 to Dec 2011. The main reason for VATS for all the patients was due to no specific diagnosis could be obtained after non-invasive methods, transbronchial lung biopsy (TBLB) examination and the consultation with pulmonologist, radiologist and pathologist. The clinical profiles, chest high resolution computerized tomography (HRCT), laboratory profile, TBLB as well as the diagnosis of before and after the VATS were analyzed. The surgery site, biopsy number, duration of the thoracic drain, post-operative complications were also recorded. The 30- and 90-day post-operative mortality rates were calculated. The risk factors associated with the incidence of post-operative complications were assessed.
RESULTS: The specific diagnosis could be established in all patients after VATS lung biopsies, with change from previous ones in 27 (84.4%). Among 20 cases (62.5%) diagnosed as unclassified ILD before the surgery, 14 (70.0%) were diagnosed as nonspecific interstitial pneumonia (NSIP), 3 (15.0%) as idiopathic pulmonary fibrosis (IPF) and 3 (15.0%) as connective tissue disease-related ILD (CTD-ILD). Among the 7 cases with complete change of diagnosis after VATS, 4 (57.1%) were cryptogenic organizing pneumonia (COP). The number of site of biopsy had no significant impact on the diagnostic efficacy. There were no significant change of vital sign and lung function after the VATS. 21 (65.6%) patients had post-operative complications, including pulmonary infection (56.3%), pulmonary atelectasis (28.1%) and pneumothorax (25.0%). The 30- and 90-day mortality rates were 0 and 5.2% respectively. Patients were divided into 2 groups based on the incidence of post-operative complications, and no significant difference was found in regards to the age, body mass index (BMI), smoking index, lung function, anesthesia method, duration of remaining the thoracic drain and the use of immunosuppressive drugs or steroids.
CONCLUSIONS: VATS is a safe and effective procedure for the diagnosis of ILD which were unclassified after routine evaluation, transbronchial lung biopsy and consultation with pulmonologist, radiologist and pathologist.

PMID: 23825760 [PubMed]

Pulmonary arterial hypertension.

Orphanet J Rare Dis. 2013 Jul 6;8(1):97

Authors: Montani D, Günther S, Dorfmüller P, Perros F, Girerd B, Garcia G, Jaïs X, Savale L, Artaud-Macari E, Price LC, Humbert M, Simonneau G, Sitbon O

Abstract
Pulmonary arterial hypertension (PAH) is a chronic and progressive disease leading to right heart failure and ultimately death if untreated. The first classification of PH was proposed in 1973. In 2008, the fourth World Symposium on PH held in Dana Point (California, USA) revised previous classifications. Currently, PH is devided into five subgroups. Group 1 includes patients suffering from idiopathic or familial PAH with or without germline mutations. Patients with a diagnosis of PAH should systematically been screened regarding to underlying mutations of BMPR2 gene (bone morphogenetic protein receptor type 2) or more rarely of ACVRL1 (activine receptor-like kinase type 1), ENG (endogline) or Smad8 genes. Pulmonary veno occusive disease and pulmonary capillary hemagiomatosis are individualized and designated as clinical group 1'. Group 2 'Pulmonary hypertension due to left heart diseases' is divided into three sub-groups: systolic dysfonction, diastolic dysfonction and valvular dysfonction. Group 3 'Pulmonary hypertension due to respiratory diseases' includes a heterogenous subgroup of respiratory diseases like PH due to pulmonary fibrosis, COPD, lung emphysema or interstitial lung disease for exemple. Group 4 includes chronic thromboembolic pulmonary hypertension without any distinction of proximal or distal forms. Group 5 regroup PH patients with unclear multifactorial mechanisms. Invasive hemodynamic assessment with right heart catheterization is requested to confirm the definite diagnosis of PH showing a resting mean pulmonary artery pressure (mPAP) of [greater than or equal to]25 mmHg and a normal pulmonary capillary wedge pressure (PCWP) of [less than or equal to]15 mmHg. The assessment of PCWP may allow the distinction between pre-capillary and post-capillary PH (PCWP [greater than or equal to] 15 mmHg). Echocardiography is an important tool in the management of patients with underlying suspicion of PH. The European Society of Cardiology and the European Respiratory Society (ESC-ERS) guidelines specify its role, essentially in the screening proposing criteria for estimating the presence of PH mainly based on tricuspid regurgitation peak velocity and systolic artery pressure (sPAP). The therapy of PAH consists of non-specific drugs including oral anticoagulation and diuretics as well as PAH specific therapy. Diuretics are one of the most important treatment in the setting of PH because right heart failure leads to fluid retention, hepatic congestion, ascites and peripheral edema. Current recommendations propose oral anticoagulation aiming for targeting an International Normalized Ratio (INR) between 1.5-2.5. Target INR for patients displaying chronic thromboembolic PH is between 2--3. Better understanding in pathophysiological mechanisms of PH over the past quarter of a century has led to the development of medical therapeutics, even though no cure for PAH exists. Several specific therapeutic agents were developed for the medical management of PAH including prostanoids (epoprostenol, trepoprostenil, iloprost), endothelin receptor antagonists (bosentan, ambrisentan, macitentan soon available) and phosphodiesterase type 5 inhibitors (sildenafil, tadalafil). This review discusses the current state of art regarding to epidemiologic aspects of PH, diagnostic approaches and the current classification of PH. In addition, currently available specific PAH therapy is discussed as well as future treatments.

PMID: 23829793 [PubMed - as supplied by publisher]