Pulmonary Pharmacology & Therapeutics

Publisher: Elsevier

Current impact factor: 2.94

Impact Factor Rankings

2016 Impact Factor Available summer 2017
2014 / 2015 Impact Factor 2.937
2013 Impact Factor 2.57
2012 Impact Factor 2.543
2011 Impact Factor 2.8
2010 Impact Factor 2.093
2009 Impact Factor 2.024
2008 Impact Factor 2.283
2007 Impact Factor 2.56
2006 Impact Factor 2.769
2005 Impact Factor 1.577
2004 Impact Factor 1.974
2003 Impact Factor 1.879
2002 Impact Factor 1.953
2001 Impact Factor 1.488
2000 Impact Factor 1.094
1999 Impact Factor 0.622
1998 Impact Factor 0.882

Impact factor over time

Impact factor

Additional details

5-year impact 2.74
Cited half-life 5.50
Immediacy index 0.64
Eigenfactor 0.00
Article influence 0.75
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


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    • Must link to publisher version with DOI
    • Author's post-print must be released with a Creative Commons Attribution Non-Commercial No Derivatives License
    • Publisher last reviewed on 03/06/2015
  • Classification

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: Purpose: QMF149 is a fixed-dose combination of the long-acting β2 agonist, indacaterol and the corticosteroid, mometasone furoate that is currently under development for treatment of patients with asthma and chronic obstructive pulmonary disease. We describe here a study designed to assess any pharmacokinetic (PK) and/or biopharmaceutical interaction between indacaterol and mometasone furoate when administered via the Breezhaler(®) device, either alone or in a free or fixed combination (QMF149) in healthy adult subjects. Methods: In this randomized, open-label, four-way crossover study, subjects were randomised to receive indacaterol acetate 150 μg, mometasone furoate 320 μg, alone and as free combination of the individual components, or QMF149 (indacaterol acetate 150 μg/mometasone furoate 320 μg) once daily for 14 days in each period, followed by a 7-day washout between periods. PK profiles were characterised on Day 14 up to 168 h post-dose. Results: Indacaterol AUC0-24h,ss and Cmax,ss after administration of QMF149 were 13% [ratio: 1.13; 90%CI: 1.09, 1.17] and 18% [ratio: 1.18; 90%CI: 1.12, 1.25] higher, respectively, than indacaterol monotherapy. Mometasone furoate AUC0-24h,ss and Cmax,ss after administration of QMF149 were 14% [ratio: 1.14; 90%CI: 1.09, 1.20] and 19% [ratio: 1.19; 90%CI: 1.13, 1.26], higher, respectively than mometasone furoate monotherapy. The majority (three of four comparisons between QMF149 and monotherapy) of the 90% confidence intervals of the between-treatment ratios for AUC0-24h,ss and Cmax,ss were within the 0.80 to 1.25 interval and therefore fulfilled bioequivalence criteria. The 90% confidence interval for Cmax,ss for MF for the QMF149 vs. monotherapy comparison was [1.13, 1.26].Although no definitive data can be provided on the basis of the present study results, it is unlikely that the small observed differences in expsoure are clinically meaningful. Multiple inhaled doses of indacaterol and mometasone furoate, when administered alone, in free combination or as QMF149 were well tolerated. Conclusions: The QMF149 fixed dose combination treatment showed comparable systemic exposure to the free combination and monotherapy treatments in terms of AUC0-24h,ss and Cmax,ss for both indacaterol and mometasone furoate, indicating an absence of clinically relevant PK or biopharmaceutical interactions. These data support further development of QMF149 without dose adjustment.
    No preview · Article · Feb 2016 · Pulmonary Pharmacology & Therapeutics
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    ABSTRACT: Background: If asthma patients fail to achieve symptom control using a medium dose of inhaled corticosteroid (ICS) alone, addition of a long-acting β2 agonist (LABA) is the preferred treatment. Currently, there are several combinations of ICS/LABA that are available, each of which has a different property. Here, we aimed to compare the early effects of budesonide/formoterol (BUD/FM; Symbicort®) for maintenance and reliever therapy (SMART) with a fixed dose of fluticasone furoate/vilanterol (FF/VI; Relvar®). Methods: Inadequately controlled asthma patients (defined as having an Asthma Control Questionnaire, 5-item version [ACQ5] score ≥1.5) with a fractional exhaled nitric oxide (FeNO) value >35 ppb, who had been treated with a medium dose of ICS alone, were enrolled. Patients were randomized into two groups and treated with two inhalations twice-daily of BUD/FM 160/4.5 μg plus as-needed BUD/FM (SMART group, n = 15) or one inhalation once-daily of FF/VI 100/25 μg plus as-needed procaterol (FF/VI group, n = 15) for 4 weeks. Outcomes including FeNO, impulse oscillometry (IOS) parameters and ACQ5 scores were measured at 0, 2 and 4 weeks. Results: Both groups showed improvement in airway inflammation, pulmonary function and symptoms from baseline to 2 weeks. From 2 to 4 weeks, the SMART group exhibited continuous improvement in most measured parameters, whereas improvement in the FF/VI group seemed to reach a plateau transiently. Consequently, the SMART group showed significant improvement in the FeNO, IOS parameters (resonance frequency and integrated area of low frequency reactance) and ACQ5 score as compared with the FF/VI group at 4 weeks. Conclusion: As compared with the FF/VI group the SMART group achieved a greater improvement in FeNO, small airway parameters regarding IOS and ACQ score, in patients with airway inflammation and uncontrolled symptoms treated with a medium dose of ICS alone. In this 4-week study, these two ICS/LABA combination therapies showed different treatment outcomes; they must be investigated further to clarify suitable patient characters and the long term efficacies for each combination.
    No preview · Article · Feb 2016 · Pulmonary Pharmacology & Therapeutics
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    ABSTRACT: Aims: To establish the dose-response relationship for pharmacodynamics (bronchodilatation), safety and pharmacokinetics of a novel particle engineered formulation of Glycopyrronium bromide (PSX1002-GB) in patients with chronic obstructive pulmonary disease (COPD). Methods: Patients with moderate to severe COPD with bronchodilator reversible lung function were enrolled into this randomized, placebo-controlled, double-blind, dose-ranging, single dose, five way cross-over study (n=37). Patients received single doses of PSX1002-GB (12.5-100μg) via pMDI with one-week washouts between treatments. Results: PSX1002-GB caused a bronchodilator response observed at 5 minutes post-dose at all doses. Significant improvements in mean change from baseline FEV1 at 24h were seen at all doses compared with placebo; Mean changes were 0.071L (95% CI 0.041-0.101), 0.087L (95% CI 0.056-0.118), 0.102L (95% CI 0.072-0.133) and 0.120L (95% CI 0.089-0.150) for 12.5, 25, 50 and 100μg respectively. PSX1002-GB 50 and 100mcg caused rapid bronchodilation at 5 mins after dosing. PSX1002-GB was well tolerated with similar adverse event rates reported compared to placebo. There were no clinically relevant changes in heart rate, blood pressure or ECG parameters (including QTc interval). Conclusion: Single doses of PSX1002-GB (12.5-100μg) were well tolerated. PSX1002-GB 50 and 100mcg delivered by pMDI produced rapid onset bronchodilation that was sustained over a 24 hour period.
    No preview · Article · Jan 2016 · Pulmonary Pharmacology & Therapeutics
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    ABSTRACT: Introduction: Secretory phospholipase A2 regulates surfactant catabolism and inflammatory cascade. This enzyme is correlated with compliance, oxygenation and major outcomes in various forms of acute respiratory failure. Steroids inhibit secretory phospholipase A2 in cell culture and are widely used to boost surfactant production before preterm delivery. No data are available about the effect of antenatal steroids on secretory phospholipase A2 in the offspring: we aimed to study this effect in a rat model of preterm lung. Material and methods: Fifteen pregnant Wistar rats were randomized to receive betamethasone, dexamethasone or placebo at 20 and 21 days gestation. Newborn rats were supported for 8h and then sacrificed: lung tissue was analysed for secretory phospholipase A2 expression and activity, inflammatory mediators and protein content. Lipidomics was analysed using liquid chromatography-mass spectrometry. Results: Secretory phospholipase A2 expression was significantly reduced by antenatal steroids (p<0.001). Secretory phospholipase A2 activity, TNFα and lysophosphatidylethanolamine, a product of phospholipase reaction, were lowest in betamethasone-treated rats (p<0.001). There was a strong correlation between secretory phospholipase A2 activity and lysophosphatidylethanolamine (r=0.75; p=0.001) and this remained significant after adjustment for total proteins or phospholipids. Conclusions: Antenatal steroids decrease secretory phospholipase A2 in rat model of preterm lung.
    No preview · Article · Dec 2015 · Pulmonary Pharmacology & Therapeutics
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    ABSTRACT: Cough in the context of interstitial lung disease (ILD) has not been the focus of many studies. However, chronic cough has a major impact on quality of life in a significant proportion of patients with ILD. For the purpose of this review, we have chosen to highlight some of the more frequently encountered diffuse lung diseases including idiopathic pulmonary fibrosis, sarcoidosis, hypersensitivity pneumonitis and systemic sclerosis associated ILD. Many of the underlying mechanisms remain speculative and further research is now required to elucidate the complex pathways involved in the pathogenesis of chronic cough in ILD. This will hopefully pave the way for the identification of new therapeutic agents to alleviate this distressing and often intractable symptom.
    No preview · Article · Nov 2015 · Pulmonary Pharmacology & Therapeutics
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    ABSTRACT: Segmental endotoxin challenge with lipopolysaccharide (LPS) can be used as a pharmacodynamic model to safely induce a transient airway inflammation in the peripheral lung of healthy subjects and to test the anti-inflammatory efficacy of investigational new drugs. In contrast to whole lung LPS challenge only a fraction of the dose is required that can be precisely administered to a specific lung region and a vehicle challenged segment as an intra-subject control can be included. The aim of this study was to assess the intra- and inter-individual variability of the response to segmental LPS challenge for the appropriate design and power calculation of future clinical trials. Two cohorts with 10 subjects each underwent two segmental LPS challenges within five weeks. The inflammatory response was evaluated in bronchoalveolar lavage (BAL) fluid at 6 (cohort 1) and 24 hours (cohort 2) both in the LPS and in a vehicle challenged segment, as well as in plasma for up to 26 hours post LPS challenge. While the cytokine response was more pronounced at 6 hours, the influx of neutrophils and monocytes dominated at 24 hours; e.g. neutrophils increased from a median (inter-quartile range, IQR) of 0.14 (0.16) and 0.09 (0.08)x10(4) cells/mL BAL fluid at baseline to 10.2 (17.1) and 19.3 (15.9)x10(4) cells/mL 24 hours after the two separate challenges. The within-subject variability was higher than the between-subject variability for most of the markers. However, sample size estimations based on the variability of outcome variables found lower or equal numbers with cross-over designs compared to parallel group designs for cellular markers at 24 hours and cytokine variables at 6 hours. The segmental LPS challenge model was safe. Future study designs have to balance between burden to the study subjects (4 versus 2 bronchoscopies), variability (within-versus between-subject), and the desired outcome variable (cells versus chemo/cytokine).
    No preview · Article · Nov 2015 · Pulmonary Pharmacology & Therapeutics
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    ABSTRACT: The diseases of the esophagus and nose are among the major factors contributing to chronic cough although their role in different patient populations is debated. Studies in animal models and in humans show that afferent C-fiber activators applied on esophageal or nasal mucosa do not initiate cough, but enhance cough induced by inhaled irritants. These results are consistent with the hypothesis that activation of esophageal and nasal C-fibers contribute to cough reflex hypersensitivity observed in chronic cough patients with gastroesophageal reflux disease (GERD) and chronic rhinitis, respectively. The afferent nerves mediating cough sensitization from the esophagus are probably the neural crest-derived vagal jugular C-fibers. In addition to their responsiveness to high concentration of acid typical for gastroesophageal reflux (pH<5), esophageal C-fibers also express receptors for activation by weakly acidic reflux such as receptors highly sensitive to acid and receptors for bile acids. The nature of sensory pathways from the nose and their activators relevant for cough sensitization are less understood. Increased cough reflex sensitivity was also reported in many patients with GERD or rhinitis who do not complain of cough indicating that additional endogenous or exogenous factors may be required to develop chronic coughing in these diseases.
    No preview · Article · Oct 2015 · Pulmonary Pharmacology & Therapeutics

  • No preview · Article · Oct 2015 · Pulmonary Pharmacology & Therapeutics
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    ABSTRACT: Background: The role of roflumilast as a potential asthma treatment is not yet fully understood. A series of placebo-controlled trials were undertaken in order to investigate the safety and efficacy of roflumilast in asthma. Aim: To evaluate the efficacy of roflumilast in nine randomized proof-of-concept, placebo-controlled monotherapy and combination therapy phase II and III clinical studies performed between 1997 and 2005. Methods: The studies were conducted at sites in Europe, North and South America, Africa, Australasia and Asia and study length varied from 4-24 weeks. Data were analyzed from 4,873 patients, 12-70 years of age, of whom 2,668 received roflumilast. At randomization patients had a forced expiratory flow (FEV1) of 45-90%. Roflumilast was investigated at doses of 125, 250 and 500μg versus placebo. In two studies, 500μg roflumilast was added on top of standard therapy with inhaled corticosteroids (ICS), 250μg fluticasone propionate, or 400μg beclomethasone dipropionate (BDP). Improvement in FEV1 from baseline was the primary endpoint in seven studies. Key secondary endpoints included asthma symptom scores and time to first severe exacerbation. Results: Roflumilast consistently improved FEV1 across the nine studies compared with placebo, reaching statistical significance in three studies. When given in addition to ICS, roflumilast provided additional improvements in FEV1 which was statistically significant for 500μg roflumilast/400μg BDP versus placebo/400μg BDP. Conclusion: Together these studies show that roflumilast has potential as an effective anti-inflammatory therapy for the treatment of asthma. Additional beneficial effects are observed when given in combination with ICS, which warrant further investigation. All studies were funded by Takeda. Trial registration numbers available on ClinicalTrials.gov: NCT00073177, NCT00076076, NCT00163527.
    No preview · Article · Oct 2015 · Pulmonary Pharmacology & Therapeutics
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    ABSTRACT: Background: Asthma-chronic obstructive pulmonary disease overlap syndrome (ACOS) is important because patients with ACOS have significantly worse outcomes compared with those with asthma or chronic obstructive pulmonary disease (COPD) alone. Inhaled corticosteroids (ICS), together with a long-acting β2 agonist (LABA), are recommended, but no therapeutic studies for ACOS have been conducted. Recently, fluticasone furoate/vilanterole (FF/VI) has been approved as the first once-daily ICS/LABA combination therapy for asthma and COPD. Methods: A 12-week, randomized, open-label cross-over study was conducted in 16 patients with ACOS to compare the effectiveness of once-daily FF/VI 200/25 μg vs. twice-daily fluticasone propionate/salmeterol (FP/SAL) 500/50 μg. The study period included a 4-week run-in, the first 4-week treatment, and the second 4-week treatment. Respiratory functions, including forced expiratory volume in one second (FEV1) and respiratory impedance using the forced oscillation technique (FOT), were measured, as was fractional exhaled nitric oxide (FeNO). A COPD assessment test (CAT) scores and asthma control test (ACT) scores were recorded 0, 4, and 8 weeks after randomization. Results: The mean values for the FEV1 were 1.33 (±0.29) L in the run-in period, 1.38 (±0.39) L after the FP/SAL treatment period, and 1.47 (±0.38) L after the FF/VI treatment period. The FEV1 value after the FF/VI treatment was significantly greater than the value after the run-in period (p < 0.01). FOT parameters, FeNO levels, CAT scores, ACT scores, and other blood tests were not significantly different during the run-in period, the FP/SAL treatment period, and the FF/VI treatment period. Conclusions: FF/VI, the first once-daily ICS/LABA, can provide substantial improvement in lung functions, indicating that FF/VI should be considered for the regular treatment of ACOS.
    No preview · Article · Oct 2015 · Pulmonary Pharmacology & Therapeutics
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    ABSTRACT: Chronic cough is a very common symptom for which patients seek medical attention but can often be difficult to manage, because associated causes may remain elusive and treatment of any associated causes does not always provide adequate relief. Current antitussives have limited efficacy and undesirable side-effects. Patients with chronic cough typically describe sensory symptoms suggestive of upper airway and laryngeal neural dysfunction. They often report cough triggered by low-level physical and chemical stimuli supporting the recently emerging concept of 'cough hypersensitivity syndrome'. Chronic cough is a neuropathic condition that could be secondary to sensory nerve damage caused by inflammatory, infective and allergic factors. Mechanisms underlying peripheral and central augmentation of the afferent cough pathways have been identified. Successful treatment of chronic cough with agents used for treating neuropathic pain, such as gabapentin and amitriptyline, would also support this concept. Further research of neuropathic cough may lead to the discovery of more effective antitussives in the future.
    No preview · Article · Oct 2015 · Pulmonary Pharmacology & Therapeutics
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    ABSTRACT: Background: Despite extensive use of inhaled corticosteroid/long-acting β2-agonist combinations in asthma, limited data evaluating dose-response for this combination class are available. The benefits of dose escalation and nature of patient subgroups likely to benefit are thus ill-defined. Method: In this randomised, double-blind, 8-week study the effects of two dose levels (100/10 and 500/20 μg b.i.d.) of a fixed combination of fluticasone/formoterol (flutiform®) were compared in 309 patients. Treatment effects upon spirometric and symptom-based endpoints were examined in the overall population and in two subgroups defined a priori by % predicted FEV1 at baseline (≥40-≤60% ["severe" airways obstruction] and >60-≤80% ["moderate" airways obstruction]). Results: No dose-response was evident for spirometric outcomes (FEV1, FEV1 AUC0-12, PEFR) either overall or in either subgroup. At variance with the spirometric data, statistically significant dose-dependent differences were seen for nocturnal outcomes and consistent numerical differences were found across multiple symptom-based outcomes (symptom scores, sleep scores, rescue medication use, asthma control days, AQLQ scores, exacerbations); greater effects were noted with the higher dose of fluticasone/formoterol. Between-group differences for the overall population were driven by treatment effect differences in the "severe" subgroup. Conclusion: In this exploratory comparison a high dose of fluticasone/formoterol in asthmatic patients appears to provide additional improvement in symptom-based rather than spirometric outcomes. Additional benefits from high versus low dose treatment are most likely in patients with severe airway obstruction, although the doses at which ceiling effects are attained may vary between individuals. Trial registration: ClinicalTrials.gov identifier: NCT00734318; EudraCT number: 2007-001633-34.
    No preview · Article · Oct 2015 · Pulmonary Pharmacology & Therapeutics
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    ABSTRACT: With fast-paced urbanization and increased energy consumption in rapidly industrialized modern China, the level of outdoor and indoor air pollution resulting from industrial and motor vehicle emissions has been increasing at an accelerated rate. Thus, there is a significant increase in the prevalence of respiratory symptoms such as coughing, wheezing, and decreased pulmonary function. Experimental exposure research and epidemiological studies have indicated that exposure to particulate matter, ozone, nitrogen dioxide, and environmental tobacco smoke have a harmful influence on development of respiratory diseases and are significantly associated with cough and wheeze. This review mainly discusses the effect of air pollutants on respiratory health, particularly with respect to cough, the links between air pollutants and microorganisms, and air pollutant sources. Particular attention is paid to studies in urban areas of China where the levels of ambient and indoor air pollution are significantly higher than World Health Organization recommendations.
    No preview · Article · Oct 2015 · Pulmonary Pharmacology & Therapeutics
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    ABSTRACT: Background: Roflumilast, a phosphodiesterase-4 inhibitor, has an established place in the treatment of chronic obstructive pulmonary disease. Its potential role as a treatment for asthma is unclear. Aim: We report the results from seven double-blind, parallel group, phase II or III studies designed to compare roflumilast with two anti-inflammatory treatments, beclomethasone dipropionate (BDP) and montelukast, in patients with asthma. Methods: The studies of 6 to 12 week duration were conducted at 309 sites in Europe, North America, South Africa and Australia from 1998 to 2005. Data from 3,802 patients, aged 12-70 years who received either roflumilast 100μg, 250μg or 500μg once daily, BDP 400μg or 500μg twice daily, or 10mg montelukast once daily was analyzed. Primary endpoints were mean change and time averaged excess area under the curve in forced expiratory volume in one second (FEV1) over the duration of the study. Secondary endpoints included change in forced vital capacity and peak expiratory flow, asthma symptoms and the concomitant use of rescue medication. Results: Roflumilast was non-inferior to BDP and montelukast and consistently increased FEV1. Use of rescue medication and all asthma symptom scores decreased significantly with all treatments, but no statistically significant between-group differences were observed. Secondary lung function endpoints generally supported the conclusions of the primary outcome measure. Conclusions: Roflumilast improves FEV1 and asthma symptoms in patients with mild to moderate asthma, and is non-inferior compared with both BDP and montelukast. It deserves further study as a potentially effective anti-inflammatory treatment for asthma.
    No preview · Article · Oct 2015 · Pulmonary Pharmacology & Therapeutics

  • No preview · Article · Sep 2015 · Pulmonary Pharmacology & Therapeutics
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    ABSTRACT: Background: Cigarette smoking is considered to be one of major causes of acute worsening of asthma as well as chronic obstructive pulmonary disease (COPD). Macrolide antibiotics have been reported to reduce the risk of exacerbations of COPD, and possibly neutrophilic asthma. However, the effect of clarithromycin (CAM) on pulmonary inflammation caused by short term exposure to cigarette smoke still remains to be investigated. Methods: C57BL/6J female mice were daily exposed to tobacco smoke using a tobacco smoke exposure system, or clean air for 8 days, while simultaneously treated with either oral CAM or vehicles. Twenty four hours after the last exposure, mice were anaesthetized and sacrificed, and bronchoalveolar lavage (BAL) fluids were collected. Cellular responses in BAL fluids were evaluated. Levels of cytokine mRNA in the lung tissues were measured by quantitative RT-PCR. Paraffin-embedded lung tissues were evaluated to quantitate degree of neutrophil infiltration. Results: The numbers of total cells, macrophages and neutrophils in the BAL fluid of smoke-exposed mice were significantly increased as compared to clean air group. These changes were significantly ameliorated in CAM-treated mice. The lung morphological analysis confirmed decrease of neutrophils by CAM treatment. Studies by quantitative PCR demonstrated CAM treatment significantly reduced lung expression levels of IL-17A, keratinocyte-derived chemokine (KC), granulocyte-macrophage colony stimulating factor (GM-CSF) and MMP-9 induced by cigarette smoke. Conclusion: We demonstrate that CAM administration resolves enhanced pulmonary inflammation induced by short term cigarette smoke exposure in mice.
    No preview · Article · Sep 2015 · Pulmonary Pharmacology & Therapeutics