Pulmonary Pharmacology &amp Therapeutics

Publisher: Elsevier

Journal description

Current impact factor: 2.54

Impact Factor Rankings

2015 Impact Factor Available summer 2015
2011 Impact Factor 2.8

Additional details

5-year impact 2.33
Cited half-life 5.00
Immediacy index 0.43
Eigenfactor 0.01
Article influence 0.71
Other titles Pulmonary pharmacology & therapeutics (Online), Pulmonary pharmacology & therapeutics, Pulmonary pharmacology and therapeutics
ISSN 1522-9629
OCLC 38867290
Material type Document, Periodical, Internet resource
Document type Internet Resource, Computer File, Journal / Magazine / Newspaper

Publisher details

Elsevier

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    • Publisher's version/PDF cannot be used
    • Articles in some journals can be made Open Access on payment of additional charge
    • NIH Authors articles will be submitted to PubMed Central after 12 months
    • Publisher last contacted on 18/10/2013
  • Classification
    ​ green

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: Vitamin D deficiency (VDD) is highly prevlalent worldwide, with adverse effects on bone health but also potentially other unfavourable consequences. VDD and asthma-incidence/severity share many common risk factors, including winter season, industrialization, poor diet, obesity, dark skin pigmentation, and high latitude. Multiple anatomical areas relevant to asthma contain both the enzyme responsible for producing activated vitamin D and the vitamin D receptor suggesting that activated vitamin D (1,25-dihydroxyvitamin D) may have important local effects at these sites. Emerging evidence suggests that VDD is associated with increased airway hyperresponsiveness, decreased pulmonary function, worse asthma control, and possibly decreased response to standard anti-asthma therapy. However the effect is inconsistent with preliminary evidence from different studies suggesting vitamin D is both beneficial and detrimental to asthma genesis and severity. Current evidence suggests that supplementation with moderate doses of vitamin D may be appropriate for maintenance of bone health in asthmatics, particularly steroid users. However emerging data from an increasing number of randomized, controlled, intervention studies of vitamin D supplementation in paediatric and adult asthma are becoming available and should help determine the importance, if any of vitamin D for asthma pathogenesis. The purpose of this second of a two-part review is to review the current human literature on vitamin D and asthma, discussing the possible consequences of VDD for asthma and the potential for vitamin D repletion as adjunct therapy. Copyright © 2015. Published by Elsevier Ltd.
    Pulmonary Pharmacology &amp Therapeutics 03/2015; DOI:10.1016/j.pupt.2015.02.010
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    ABSTRACT: Geranylgeranylacetone (GGA) has been clinically used as an anti-ulcer drug. In the present study, we explored the protective effects of GGA on lung ischemia/reperfusion injury (IRI) and the underlying mechanism. The results demonstrated that GGA ameliorated the lung biochemical and histological alterations induced by IRI, which was reversed by HSP70 inhibition. To further explore the mechanism of GGA action, we focused on NF-kB and thioredoxin (Trx) redox system. It was shown that GGA induced the HSP70 and Trx-1 expression, NF-kB nuclear translocation and activated thioredoxin reductase (TrxR). The Trx-1 expression and TrxR activity was suppressed by HSP70 and NF-kB inhibition, while the nuclear NF-kB p65 expression was suppressed by HSP70 inhibitor. These results indicated that GGA may protect rat lung against IRI by HSP70 and Trx redox system, in which NF-kB pathway may be involved. Copyright © 2015. Published by Elsevier Ltd.
    Pulmonary Pharmacology &amp Therapeutics 03/2015; DOI:10.1016/j.pupt.2015.02.009
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    ABSTRACT: Vitamin D deficiency (VDD) is highly prevlalent worldwide. The classical role for vitamin D is to regulate calcium absorption form the gastrointestinal tract and influence bone health. Recently vitamin D receptors and vitamin D metabolic enzymes have been discovered in numerous sites systemically supporting diverse extra-skeletal roles of vitamin D, for example in asthmatic disease. Further, VDD and asthma share several common risk factors including high latitude, winter season, industrialization, poor diet, obesity, and dark skin pigmentation. Vitamin D has been demonstrated to possess potent immunomodulatory effects, including effects on T cells and B cells as well as increasing production of antimicrobial peptides (e.g. cathelicidin). This immunomodulation may lead to asthma specific clinical benefits in terms of decreased bacterial/viral infections, altered airway smooth muscle-remodeling and -function as well as modulation of response to standard anti-asthma therapy (e.g. glucocorticoids and immunotherapy). Thus, vitamin D and its deficiency have a number of biological effects that are potentially important in altering the course of disease pathogenesis and severity in asthma. The purpose of this first of a two-part review is to review potential mechanisms whereby altering vitamin D status may influence asthmatic disease. Copyright © 2015. Published by Elsevier Ltd.
    Pulmonary Pharmacology &amp Therapeutics 02/2015; DOI:10.1016/j.pupt.2015.02.004
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    ABSTRACT: The long-acting inhaled bronchodilators available for use in chronic obstructive pulmonary disease (COPD) vary in their pharmacological class (β2-adrenergic agonist or antimuscarinic/anticholinergic, alone or combined), durations of action and speed of onset of bronchodilator effect. In the early stages of development of a maintenance bronchodilator, the goals are to identify a molecule with the theoretically 'ideal' profile of fast onset and prolonged duration of action in comparison with existing agents, while minimizing non-specific activity at organs outside the lungs. The move towards increasing duration of bronchodilator action is generally paralleled by improved effects on clinical outcomes, and the advent of more potent agents seems likely to provide an opportunity to reduce overreliance on the use of inhaled corticosteroids in treating COPD. In terms of onset of action, an immediately perceived benefit in reducing dyspnea, although not definitively demonstrated, might prove useful in increasing adherence, which is very poor among patients with COPD. Once-daily administration may also be helpful in this respect. Shared decision-making between patient and physician in the choice of treatment is important in optimizing adherence and, thus, treatment effectiveness. Copyright © 2015. Published by Elsevier Ltd.
    Pulmonary Pharmacology &amp Therapeutics 02/2015; DOI:10.1016/j.pupt.2015.02.007
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    ABSTRACT: Inhalation is the preferred route of drug administration in chronic respiratory diseases because it optimises delivery of the active compounds to the targeted site and minimises side effects from systemic distribution. The choice of a device should be made after careful evaluation of the patient's clinical condition (degree of airway obstruction, comorbidities), as well as their ability to coordinate the inhalation manoeuvre and to generate sufficient inspiratory flow. These patient factors must be aligned with the specific advantages and limitations of each inhaler when making this important choice. Finally, adherence to treatment is not the responsibility of the patient alone, but should be shared also by clinicians. Clinicians have access to a wide selection of pressurised metered dose inhalers (pMDIs) and dry powder inhalers (DPIs) that can be used effectively when matched to the needs of individual patients; this should be perceived as an opportunity rather than a limitation. Copyright © 2015. Published by Elsevier Ltd.
    Pulmonary Pharmacology &amp Therapeutics 02/2015; DOI:10.1016/j.pupt.2015.02.006
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    ABSTRACT: Reduced innate immunity responses as well as reduced T regulatory activities characterise bronchial asthma. In this study the effect of budesonide on the expression of TLR4 and TLR2 in T regulatory lymphocyte sub-population was assessed. TLR4 and TLR2 expression in total peripheral blood mononuclear cells (PBMC), in CD4+/CD25+ and in CD4+/CD25-was evaluated, by flow cytometric analysis, in mild intermittent asthmatics (n=14) and in controls (n=11). The in vitro effects of budesonide in modulating: TLR4 and TLR2 expression in controls and in asthmatics; IL-10 expression and cytokine release (IL-6 and TNF-α selected by a multiplex assay) in asthmatics were also explored. TLR4 and TLR2 were reduced in total PBMC from asthmatics in comparison to PBMC from controls. CD4+CD25+ cells expressed at higher extent TLR2 and TLR4 in comparison to CD4+CD25-cells. Budesonide was able to increase the expression of TLR4, TLR2 and IL-10 in CD4+/CD25highly+ cells from asthmatics. TLR4 ligand, LPS induced Foxp3 expression. Budesonide was also able to reduce the release of IL-6 and TNF-α by PBMC of asthmatics. Budesonide potentiates the activity of Treg by increasing TLR4, TLR2 and IL-10 expression. This event is associated to the decreased release of IL-6 and ΤΝF-α in PBMC treated with budesonide. These findings shed light on new mechanisms by which corticosteroids, drugs widely used for the clinical management of bronchial asthma, control T lymphocyte activation. Copyright © 2015. Published by Elsevier Ltd.
    Pulmonary Pharmacology &amp Therapeutics 02/2015; DOI:10.1016/j.pupt.2015.02.003
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    ABSTRACT: Inhalation of agricultural occupational dusts from swine confinement facilities can result in lung inflammation. The innate immune response to organic barn dusts results in production of a number of pro-inflammatory factors in the lungs of barn workers such as cytokines, chemokines, and an influx of neutrophils. Many of these inflammatory factors are influenced by the chemokine CXCL8/IL-8 (KC or MIP-2 in mice). Previously, we have demonstrated that an endotoxin-independent component of swine barn dust extract (SBE) elevates lung chemokines in a protein kinase C (PKC)-dependent manner resulting in the significant formation of lung inflammatory cell infiltrates in a mouse model of SBE injury. In this study we test the ability of a CXCR1/CXCR2 antagonist, CXCL8(3-74)K11R/G31P (G31P) to block many of the features of lung-inflammation in response to challenge with SBE in an established mouse exposure system. Injection of G31P concurrent with SBE nasal instillation over a course of 3 weeks significantly reduced neutrophil accumulation in the lungs of barn dust exposed animals compared to those given SBE alone. There was a similar reduction in pro-inflammatory cytokines and chemokines IL-6, KC, and MIP-2 in SBE plus G31P-treated mice. In addition to excreted products, the receptors ICAM-1, CXCR1, and CXCR2, which all were elevated with SBE exposure, were also decreased with G31P treatment. SBE activation of PKCα and PKCε was reduced as well with G31P treatment. Thus, G31P was found to be highly effective at reducing several features of lung inflammation in mice exposed to barn dust extracts.
    Pulmonary Pharmacology &amp Therapeutics 02/2015; 31. DOI:10.1016/j.pupt.2015.02.002
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    ABSTRACT: Cough is one of the most common reasons that patients seek medical attention. Cough guidelines from numerous countries and societies are available to assist the clinician to investigate and manage patients with cough. We review some of the recent progress in the field of cough that may lead to revision of these guidelines. In adults with chronic cough, new causes such as obstructive sleep apnoea have been identified. A new terminology, cough hypersensitivity syndrome (CHS), has been proposed for patients with chronic cough, which emphasises cough reflex hypersensitivity as a key feature. New therapeutic options are now available, particularly for patients with refractory or idiopathic chronic cough, which include gabapentin, speech pathology management and morphine. There has been great progress in the assessment of cough with the development of validated quality of life questionnaires and cough frequency monitoring tools. In children, common aetiologies differ from adults and those managed according to guidelines have better outcomes compared to usual care. New diagnostic entities such as protracted bacterial bronchitis have been described. Paediatric-specific cough assessment tools such as the Parent/Child Quality of Life Questionnaire will help improve the assessment of patients. Further research is necessary to improve the evidence base for future clinical guideline recommendations. Guidelines in future should also aim to reach a wider audience that includes primary care physicians, non-specialists and patients. Copyright © 2015. Published by Elsevier Ltd.
    Pulmonary Pharmacology &amp Therapeutics 02/2015; DOI:10.1016/j.pupt.2015.01.007
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    ABSTRACT: Chronic obstructive pulmonary disease (COPD) is characterized by neutrophil-dominated airway mucosal inflammation and elevated neutrophil counts in sputum and lung tissue. CXC chemokine receptor 2 (CXCR2) is predominantly expressed on neutrophils and mediates the migration of neutrophils to inflammatory sites. AZD5069 is a small molecule CXCR2 antagonist with the potential to inhibit neutrophil migration into the airways in patients with COPD. This 4-week, randomized, double-blind, placebo-controlled, parallel-group, multi-center, Phase IIa study evaluated the safety and tolerability of AZD5069 in patients with moderate-to-severe COPD (ClinicalTrials.gov identifier: NCT01233232). The pharmacokinetics and effect of AZD5069 on blood neutrophil counts were also assessed. Patients completed daily diary cards and attended weekly clinic visits for safety assessments. 87 patients (mean FEV1 56% pred; mean age 64 years; 69% male) were randomized to receive placebo (n=29), AZD5069 50 mg bid (n=30) or AZD5069 80 mg bid (n=28) for 4 weeks. AZD5069 was well tolerated with adverse events (AEs) reported in 9 (31%), 10 (33%) and 6 (21%) patients in the placebo, AZD5069 50 mg and AZD5069 80 mg groups, respectively. AEs were generally mild or moderate in severity. The incidence of infections, the most commonly reported AE, was similar across the three groups (17%, 17% and 11% of patients in the placebo, AZD5069 50 and 80 mg groups, respectively). Blood neutrophil counts decreased on average from baseline by 14-40% and 13-36% in the AZD5069 50 mg and 80 mg groups, respectively, and 4 patients discontinued from the study due to decreased neutrophil count, 3 in the AZD5069 50 mg group and 1 in the 80 mg group. The systemic exposure (AUC and Cmax) of AZD5069 increased less than in proportion to the dose and there was a large overlap in the individual exposures between the two dose levels. AZD5069 was well tolerated overall in those patients who completed study treatment, with no increase in infection rates in either dosage group compared with placebo. Further studies with AZD5069 appear to be warranted. Copyright © 2015. Published by Elsevier Ltd.
    Pulmonary Pharmacology &amp Therapeutics 02/2015; 31. DOI:10.1016/j.pupt.2015.02.001
  • Pulmonary Pharmacology &amp Therapeutics 02/2015; 31. DOI:10.1016/j.pupt.2015.01.003
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    ABSTRACT: To determine the effects of montelukast added to maintenance inhaled steroids (ICS) therapy during the school year in children with stable asthma on the ICS use, frequency of exacerbations, lung function, asthma symptoms, fractional exhaled nitric oxide (FeNO) level and exercise-induced bronchoconstriction (EIB). Seventy six asthmatic children aged 6-14 years, allergic to house dust mites were randomized to a double-blinded trial comparing montelukast therapy to a matching placebo. We studied following end-points: the reduction in the ICS dose, the frequency of exacerbations, lung function, asthma control test score, and the change from baseline in FEV1 during a standardized exercise treadmill challenge. ICS dose was adjusted in a stepwise fashion to determine the lowest dose necessary to control asthma symptoms. We showed that children with baseline value of FeNO above 31 ppb and well controlled asthma symptoms on low doses of ICS, benefit the most from additive therapy with montelukast; their cumulative ICS dose is lower than in children treated with ICS only. Also, the addition of montelukast to regular treatment in asthmatic children resulted in a significant reduction in the frequency of exacerbations and EIB protection. It is reasonable to add montelukast to ICS therapy in asthmatic children during the school year, to lower cumulative ICS dose in children with well controlled asthma symptoms, as well as to reduce number of exacerbations, and to achieve better control of EIB. NCT01266772. Copyright © 2015. Published by Elsevier Ltd.
    Pulmonary Pharmacology &amp Therapeutics 01/2015; 31. DOI:10.1016/j.pupt.2015.01.004
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    ABSTRACT: Randomized clinical trials (RCTs) are the gold standard for the assessment of any therapeutic intervention. Real-life (R-L) studies are needed to verify the provided results beyond the experimental setting. This review aims at comparing RCTs and R-L studies on omalizumab in adult severe allergic asthma, in order to highlight the concurring results and the discordant/missing data. The results of a selective literature research, including "omalizumab, controlled studies, randomized trial, real-life studies" as key words are discussed. Though some similarities between RCTs and R-L studies strengthen omalizumab efficacy and safety outcomes, significant differences concerning study population features, follow-up duration, local adverse events and drop-out rate for treatment inefficacy emerge between the two study categories. Furthermore the comparative analysis between RCTs and R-L studies highlights the need for further research, concerning in particular long-term effects of omalizumab and its impact on asthma comorbidities. Copyright © 2015. Published by Elsevier Ltd.
    Pulmonary Pharmacology &amp Therapeutics 01/2015; 31. DOI:10.1016/j.pupt.2015.01.006
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    ABSTRACT: Statins have pleiotropic immunomodulatory effects that may be beneficial in the treatment of asthma. We previously reported that treatment with atorvastatin improved asthma symptoms in smokers with asthma in the absence of a change in the concentration of a selection of sputum inflammatory mediators. To determine the effects of atorvastatin alone and in combination with inhaled corticosteroid on a range of sputum cytokines, chemokines and growth factors implicated in the pathogenesis of asthma, and their association with asthma control questionnaire (ACQ) and/or asthma quality of life questionnaire (AQLQ) scores. Sputum samples were analyzed from a sub-group of 39 smokers with mild to moderate asthma recruited to a randomized controlled trial comparing atorvastatin (40 mg/day) versus placebo for four weeks, followed by inhaled beclometasone (400 μg/day) for a further four weeks. Induced sputum supernatant fluid was analysed (Luminex or biochemical analyses) for concentrations of 35 mediators. Sputum mediator concentrations were not reduced by inhaled beclometasone alone. Atorvastatin significantly reduced sputum concentrations of CCL7, IL-12p70, sCD40L, FGF-2, CCL4, TGF-α and MMP-8 compared with placebo and, when combined with inhaled beclometasone, reduced sputum concentrations of MMP-8, IL-1β, IL-10, MMP-9, sCD40L, FGF-2, IL-7, G-CSF and CCL7 compared to ICS alone. Improvements in ACQ and/or AQLQ scores with atorvastatin and ICS were associated with decreases in G-CSF, IL-7, CCL2 and CXCL8. Short-term treatment with atorvastatin alone or in combination with inhaled beclometasone reduces several sputum cytokines, chemokines and growth factors concentrations unresponsive to inhaled corticosteroids alone, in smokers with asthma. Copyright © 2015. Published by Elsevier Ltd.
    Pulmonary Pharmacology &amp Therapeutics 01/2015; 31. DOI:10.1016/j.pupt.2015.01.001
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    ABSTRACT: Chronic obstructive pulmonary disease (COPD) is currently the fourth leading cause of death worldwide and, in contrast to the trend for cardiovascular diseases, mortality rates still continue to climb. This increase is in part due to an ageing population, being expanded by the “Baby boomer” generation who grew up when smoking rates were at their peak and by people in developing countries living longer. Sadly, there has been a disheartening lack of new therapeutic approaches to counteract the progressive decline in lung function associated with the disease that leads to disability and death. COPD is characterized by irreversible chronic airflow limitation that is caused by emphysematous destruction of lung elastic tissue and/or obstruction in the small airways due to occlusion of their lumen by inflammatory mucus exudates, narrowing and obliteration. These lesions are mainly produced by the response of the tissue to the repetitive inhalational injury inflicted by noxious gases, including cigarette smoke, which involves interaction between infiltrating inflammatory immune cells, resident cells (e.g. epithelial cells and fibroblasts) and the extra cellular matrix. This interaction leads to tissue destruction and airway remodeling with changes in elastin and collagen, such that the epithelial-mesenchymal trophic unit is dysregulated in both the disease pathologies. This review focuses on: 1- novel inflammatory and remodeling factors that are altered in COPD; 2- in vitro and in vivo models to understand the mechanism whereby the extra cellular matrix environment in altered in COPD; and 3- COPD in the context of wound-repair tissue responses, with a focus on the regulation of mesenchymal cell fate and phenotype.
    Pulmonary Pharmacology &amp Therapeutics 12/2014; DOI:10.1016/j.pupt.2014.04.004