Efficacy and safety of a first-in-class inhaled PDE3/4 inhibitor (ensifentrine) vs salbutamol in asthma
This study aimed to investigate the dose-response and pharmacology of a range of single doses of nebulised ensifentrine (RPL554), an inhaled dual phosphodiesterase (PDE) 3/4 inhibitor in patients with asthma.MethodsIn this randomised, placebo-controlled, double-blind crossover study, patients received single nebulised doses of ensifentrine 0.4, 1.5, 6 and 24 mg, salbutamol 2.5 and 7.5 mg, and placebo. Eligible patients were adults with asthma, pre-bronchodilator forced expiratory volume in 1 s (FEV1) 60–90% predicted and ≥1.5 L, with post-salbutamol FEV1 increase ≥15%. The co-primary objectives were pea...
Source: Pulmonary Pharmacology and Therapeutics - June 15, 2019 Category: Respiratory Medicine Source Type: research

Pharmacokinetics of ambrisentan in a patient with Pulmonary Arterial Hypertension and a total gastrectomy
Publication date: Available online 12 June 2019Source: Pulmonary Pharmacology & TherapeuticsAuthor(s): Eric Abston, Harrison W. FarberAbstractSignificant advances have been made in the treatment of arterial pulmonary hypertension (PAH). However, no studies to date have assessed the impact of altered gastrointestinal (GI) anatomy or absorption on the efficacy and bioavailability of oral medications in the treatment of PAH. Here, we describe the treatment of a patient with PAH initially treated with epoprostenol. Subsequently, an intractable upper GI bleed required a total gastrectomy. With epoprostenol, there was near n...
Source: Pulmonary Pharmacology and Therapeutics - June 12, 2019 Category: Respiratory Medicine Source Type: research

Fevipiprant has a low risk of influencing co-medication pharmacokinetics: Impact on simvastatin and rosuvastatin in different SLCO1B1 genotypes
Publication date: Available online 10 June 2019Source: Pulmonary Pharmacology & TherapeuticsAuthor(s): Birk Poller, Ralph Woessner, Avantika Barve, Hanns-Christian Tillmann, Janardhana Vemula, Alexandra Nica, Walid Elbast, Hilmar Schiller, Peter End, Gian Camenisch, Markus WeissAbstractFevipiprant, a prostaglandin D2 receptor 2 antagonist, is in clinical development as a treatment for asthma. The goal of this study was to assess the potential of fevipiprant to cause drug-drug interactions (DDI) as a perpetrator, that is, by altering the pharmacokinetics (PK) of co-medications.In vitro drug interaction studies of clinic...
Source: Pulmonary Pharmacology and Therapeutics - June 12, 2019 Category: Respiratory Medicine Source Type: research

Characteristics of Chinese chronic cough patients
Publication date: Available online 6 June 2019Source: Pulmonary Pharmacology & TherapeuticsAuthor(s): Li Long, Kefang LaiAbstractChronic cough is one of the most common complains for patients seeking medical attention in both general practice and respiratory specialist clinics. Cough variant asthma, eosinophilic bronchitis, upper airway cough syndrome, as well as gastro-esophageal reflux disease are common conditions associated with chronic cough, and cough variant asthma, eosinophilic bronchitis account for a higher proportion of patients with chronic cough in China than in Western countries. An older female predomina...
Source: Pulmonary Pharmacology and Therapeutics - June 7, 2019 Category: Respiratory Medicine Source Type: research

Bronchiectasis and cough: An old relationship in need of renewed attention
Publication date: Available online 6 June 2019Source: Pulmonary Pharmacology & TherapeuticsAuthor(s): Micheál Mac Aogáin, Sanjay Haresh ChotirmallAbstractBronchiectasis is an increasingly recognised respiratory condition with limited therapeutic options and a complex spectrum of clinical manifestations that invariably includes chronic cough. As the primary presentation of bronchiectasis in most cases, chronic cough and its mechanistic underpinnings are of central importance but remain poorly understood in this setting. Bronchiectasis is also increasingly identified as an underlying cause of chronic cough ...
Source: Pulmonary Pharmacology and Therapeutics - June 7, 2019 Category: Respiratory Medicine Source Type: research

Nicotinic receptor dependent regulation of cough and other airway defensive reflexes
We present evidence that these nicotinic receptors are components of essential transducing and encoding mechanisms regulating airway defense. (Source: Pulmonary Pharmacology and Therapeutics)
Source: Pulmonary Pharmacology and Therapeutics - June 7, 2019 Category: Respiratory Medicine Source Type: research

Cardiovascular safety of revefenacin, a once-daily, lung-selective, long-acting muscarinic antagonist for nebulized therapy of chronic obstructive pulmonary disease: Evaluation in phase 3 clinical trials
Publication date: Available online 30 May 2019Source: Pulmonary Pharmacology & TherapeuticsAuthor(s): James F. Donohue, Gregory Feldman, Sanjay Sethi, Chris N. Barnes, Srikanth Pendyala, David Bourdet, Glenn CraterAbstractThe cardiovascular safety of revefenacin, an anticholinergic indicated for the maintenance treatment of patients with chronic obstructive lung disease (COPD), was evaluated in phase 3 trials in patients with moderate to very severe COPD. No clinically meaningful changes in 12-lead electrocardiogram recordings were observed with up to 52 weeks of once-daily revefenacin 88 or 175 μg. In a pooled an...
Source: Pulmonary Pharmacology and Therapeutics - May 31, 2019 Category: Respiratory Medicine Source Type: research

Interaction between blood lead level and chronic obstructive pulmonary disease (COPD) on risk of heart attack or stroke: USA NHANES, 2013–2014
ConclusionsThe low lead level today means more effect of COPD on the occurrence of heart attack and stroke. More studies required to understand the pathways of the association of COPD, CVD and lead due to their shared risk factors. (Source: Pulmonary Pharmacology and Therapeutics)
Source: Pulmonary Pharmacology and Therapeutics - May 19, 2019 Category: Respiratory Medicine Source Type: research

Intra-tracheal amikacin spray delivery in healthy mechanically ventilated piglets
ConclusionNebulization remains the most reliable and simple technique to deliver inhaled amikacin uniformly to the lung during mechanical ventilation. Further development of tracheal sprays is required to take advantage of potential benefits related to high drug output and low extra-pulmonary deposition in large animals. (Source: Pulmonary Pharmacology and Therapeutics)
Source: Pulmonary Pharmacology and Therapeutics - May 16, 2019 Category: Respiratory Medicine Source Type: research

Are neural pathways processing airway inputs sensitized in patients with cough hypersensitivity?
Publication date: Available online 15 May 2019Source: Pulmonary Pharmacology & TherapeuticsAuthor(s): Michael J. Farrell, Stuart B. MazzoneAbstractPatients with cough hypersensitivity exhibit unusually low thresholds for responses to tussive stimuli, exaggerated responses to suprathreshold tussive stimuli, and report spontaneous experiences of urge-to-cough in the absence of exogenous stimulation. These aberrant responses to tussive challenge have the hallmark features of behaviours associated with a sensitized sensory system. Searching for further evidence to implicate neural sensitization in the symptomatology of cou...
Source: Pulmonary Pharmacology and Therapeutics - May 15, 2019 Category: Respiratory Medicine Source Type: research

Editorial Board
Publication date: June 2019Source: Pulmonary Pharmacology & Therapeutics, Volume 56Author(s): (Source: Pulmonary Pharmacology and Therapeutics)
Source: Pulmonary Pharmacology and Therapeutics - May 15, 2019 Category: Respiratory Medicine Source Type: research

Efficacy and safety of the dual bronchodilator combination umeclidinium/vilanterol in COPD by age and airflow limitation severity: A pooled post hoc analysis of seven clinical trials
This study compared the efficacy and safety of a long-acting muscarinic antagonist/long-acting β2-agonist dry powder combination in elderly patients with COPD and patients with moderate-to-very severe airflow limitation.MethodsThis post hoc pooled analysis of seven randomized studies of ≥12 weeks’ duration investigated the efficacy and safety of umeclidinium/vilanterol (UMEC/VI) 62.5/25 μg versus tiotropium (TIO) 18 μg or fluticasone propionate/salmeterol (FP/SAL) 250/50 μg. Change from baseline in trough forced expiratory volume in 1 s (FEV1), a common efficacy measure in all trials, proport...
Source: Pulmonary Pharmacology and Therapeutics - May 14, 2019 Category: Respiratory Medicine Source Type: research

Airway hypersensitivity induced by eosinophil granule-derived cationic proteins
Publication date: Available online 13 May 2019Source: Pulmonary Pharmacology & TherapeuticsAuthor(s): Lu-Yuan Lee, Qihai Gu, An-Hsuan Lin, Mehdi Khosravi, Gerald GleichAbstractVagal bronchopulmonary C-fiber sensory nerves play an important role in the manifestation of airway hypersensitivity, a common and prominent pathophysiological feature of airway inflammatory diseases. Eosinophil granule-derived cationic proteins are known to be involved in the mucosal damage and development of bronchial hyperresponsiveness during allergic airway inflammation. In view of these background information, we have carried out a series o...
Source: Pulmonary Pharmacology and Therapeutics - May 14, 2019 Category: Respiratory Medicine Source Type: research

Probucol ameliorates EMT and lung fibrosis through restoration of SIRT3 expression
Publication date: Available online 11 May 2019Source: Pulmonary Pharmacology & TherapeuticsAuthor(s): Hong-Xia Zhang, Yi-Nan Li, Xiu-Li Wang, Chang-Lin Ye, Xiao-Yan Zhu, Hui-Ping Li, Tao Yang, Yu-Jian LiuAbstractPulmonary fibrosis is a progressive fibrotic lung disease with a paucity of therapeutic options. Here we investigated the potential roles of probucol, a cholesterol-lowering drug with potent anti-oxidation properties, on pulmonary epithelial-mesenchymal transition (EMT) and fibrosis. We found that bleomycin-induced lung fibrosis was associated with increased transforming growth factor (TGF)-β1, α-smo...
Source: Pulmonary Pharmacology and Therapeutics - May 13, 2019 Category: Respiratory Medicine Source Type: research

Assessing laryngeal function and hypersensitivity
Publication date: Available online 18 April 2019Source: Pulmonary Pharmacology & TherapeuticsAuthor(s): B. Famokunwa, E.S. Walsted, J.H. HullAbstractThe larynx is one of the most highly innervated organs in humans, adapted to simultaneously deliver several key respiratory functions including airway protection, swallowing and phonation. In some individuals the larynx can adopt a state that could be considered ‘dysfunctional’ or maladaptive; resulting in or contributing to a range of clinical disorders such as chronic refractory cough, inducible laryngeal obstruction (previously termed paradoxical vocal fold ...
Source: Pulmonary Pharmacology and Therapeutics - April 19, 2019 Category: Respiratory Medicine Source Type: research

Dual role of autophagy/mitophagy in chronic obstructive pulmonary disease
Publication date: Available online 17 April 2019Source: Pulmonary Pharmacology & TherapeuticsAuthor(s): Shan Jiang, Jing Sun, Nabijan Mohammadtursun, Zhang Hu, Qiuping Li, Zhengxiao Zhao, Hongying Zhang, Jingcheng DongAbstractChronic obstructive pulmonary disease (COPD) is a common lung disease characterised by progressive, irreversible airflow limitation. Multiple regulatory pathways are involved in COPD pathogenesis. Emerging evidence from clinical and basic medical research has suggested that autophagy—a highly conserved catabolic process mediated under various cellular stress conditions—plays a role in ...
Source: Pulmonary Pharmacology and Therapeutics - April 17, 2019 Category: Respiratory Medicine Source Type: research

Outcomes of fibrinolytic therapy for patients with metastatic cancer and acute pulmonary embolism
Publication date: Available online 5 April 2019Source: Pulmonary Pharmacology & TherapeuticsAuthor(s): Gbolahan O. Ogunbayo, Robert Pecha, Naoki Misumida, Elliott Goodwin, Karam Ayoub, Dustin Hillerson, Ayman Elbadawi, Ahmed Abdel-latif, Claude S. Elayi, Adrian W. Messerli, Susan S. SmythAbstractIntroductionMalignancy is a common cause of morbidity and mortality in the United States and around the world and the second leading cause of death in the United States. There is little data on the impact of metastatic cancer on the risk of hemorrhagic stroke or mortality among patients undergoing fibrinolytic therapy (FT) for ...
Source: Pulmonary Pharmacology and Therapeutics - April 6, 2019 Category: Respiratory Medicine Source Type: research

Systemic treatment with resveratrol alleviates adjuvant arthritis-interstitial lung disease in rats via modulation of JAK/STAT/RANKL signaling pathway
Publication date: Available online 28 March 2019Source: Pulmonary Pharmacology & TherapeuticsAuthor(s): Guangxia Yang, Lei Lyu, Xinhua Wang, Liang Bao, Beili Lyu, Zikai LinAbstractInterstitial lung disease (ILD) is the most common pulmonary manifestation of Rheumatoid arthritis (RA) lung disease. The mechanism of RA-ILD remains obscure and more effective treatments are still needed. Resveratrol (RSV) a phytoalexin found with anti-inflammation and antioxidant activity. RSV has been reported to protect against RA. In current study, we evaluated the effects of RSV on RA-ILD and further explored the underlying mechanisms. ...
Source: Pulmonary Pharmacology and Therapeutics - March 29, 2019 Category: Respiratory Medicine Source Type: research

Idiopathic pulmonary fibrosis-associated cough: Mechanisms and management
Publication date: Available online 28 March 2019Source: Pulmonary Pharmacology & TherapeuticsAuthor(s): Katherine Myall, Joanne E. Kavanagh, Surinder S. Birring (Source: Pulmonary Pharmacology and Therapeutics)
Source: Pulmonary Pharmacology and Therapeutics - March 29, 2019 Category: Respiratory Medicine Source Type: research

Implementing an interstitial lung disease clinic improves survival without increasing health care resource utilization
ConclusionsSpecialized, multi-disciplinary ILD care in a dedicated regional clinic is associated with improved survival and does not cause an increase of HRU, supporting the institution of potentially more cost-effective care with specialized ILD clinics. (Source: Pulmonary Pharmacology and Therapeutics)
Source: Pulmonary Pharmacology and Therapeutics - March 29, 2019 Category: Respiratory Medicine Source Type: research

Safety and efficacy of the human neutrophil elastase inhibitor BAY 85-8501 for the treatment of non-cystic fibrosis bronchiectasis: a randomized controlled trial
Conclusions1 mg BAY 85-8501 OD had a favourable safety and tolerability profile when administered for 28 days to patients with non-CF BE. Further studies with a longer treatment duration are needed to evaluate the potential clinical efficacy in this study population. (Source: Pulmonary Pharmacology and Therapeutics)
Source: Pulmonary Pharmacology and Therapeutics - March 25, 2019 Category: Respiratory Medicine Source Type: research

Chronic cough in the elderly
Publication date: Available online 23 March 2019Source: Pulmonary Pharmacology & TherapeuticsAuthor(s): Woo-Jung Song, Ha-Kyeong Won, Jin An, Sung-Yoon Kang, Eun-Jung Jo, Yoon-Seok Chang, Byung-Jae Lee, Sang-Heon ChoAbstractChronic cough is a multi-factorial syndrome commonly presenting as cough hypersensitivity in adult patients. It is a common medical condition in the communities but is more prevalent in older adults. Elderly patients (≥65 years) frequently suffer from multiple comorbidities, which may lead to more clinical heterogeneity in chronic cough and pose diagnostic and therapeutic challenges. Hyposensitiv...
Source: Pulmonary Pharmacology and Therapeutics - March 24, 2019 Category: Respiratory Medicine Source Type: research

BLU-5937: A selective P2X3 antagonist with potent anti-tussive effect and no taste alteration
In conclusion, BLU-5937 was selected as a drug candidate for the treatment of chronic cough due to its high potency and selectivity for P2X3 homotrimeric receptors, strong anti-tussive effects, excellent tolerability and predicted pharmacokinetic properties in humans. (Source: Pulmonary Pharmacology and Therapeutics)
Source: Pulmonary Pharmacology and Therapeutics - March 20, 2019 Category: Respiratory Medicine Source Type: research

Update on the clinical development of gefapixant, a P2X3 receptor antagonist for the treatment of refractory chronic cough
Publication date: Available online 14 March 2019Source: Pulmonary Pharmacology & TherapeuticsAuthor(s): David Muccino, Stuart GreenAbstractChronic cough, or cough lasting>8 weeks, is often associated with underlying medical conditions (ie, asthma, gastroesophageal reflux disease, nonasthmatic eosinophilic bronchitis, and upper-airway cough syndrome). In some patients with chronic cough, treatment of these underlying conditions does not resolve the cough (refractory chronic cough [RCC]), or none of these conditions are present (unexplained chronic cough [UCC]). Despite appropriate medical evaluation, patients with RC...
Source: Pulmonary Pharmacology and Therapeutics - March 16, 2019 Category: Respiratory Medicine Source Type: research

Long acting β2-agonist's activation of cyclic AMP cannot halt ongoing mitogenic stimulation in airway smooth muscle cells
This study compared the anti-proliferative effect of LABA in human primary ASMC, in situations where LABA were applied before, together, or after platelet derived growth factor (PDGF-BB). Cells obtained from controls (n = 5), and asthma patients (n = 5) were stimulated by PDGF-BB (10 ng/ml) before or after the application of formoterol or salmeterol. Proliferation was determined by direct cell counts over three days, cell cycle control proteins p21(Waf1/Cip1), p27(Kip1), signalling proteins Erk1/2 and p38 mitogen activated protein kinase (MAPK) were detected by immuno-blotting. PDGF-BB induced proliferation was s...
Source: Pulmonary Pharmacology and Therapeutics - March 13, 2019 Category: Respiratory Medicine Source Type: research

Pharmacological characterization of the interaction between tiotropium bromide and olodaterol on human bronchi and small airways
In this study we have characterized the interaction between the LAMA, tiotropium bromide, and the LABA, olodaterol, on the contractile tone of human medium bronchi and small airways. The response to a combination of tiotropium bromide and olodaterol was assessed at sub-maximal contractile tone induced by carbachol. The duration of action was studied in tissue contracted by transmural stimulation. Relaxation of bronchial tone was expressed as % of maximal response to papaverine. Drug interactions were analyzed by the Bliss Independence method and Unified Theory. Tiotropium bromide/olodaterol combinations induced a significa...
Source: Pulmonary Pharmacology and Therapeutics - March 12, 2019 Category: Respiratory Medicine Source Type: research

Targeting C-fibers for peripheral acting anti-tussive drugs
Publication date: Available online 11 March 2019Source: Pulmonary Pharmacology & TherapeuticsAuthor(s): Mayur J. Patil, Hui Sun, Fei Ru, Sonya Meeker, Bradley J. UndemAbstractActivation of vagal C-fibers is likely involved in some types of pathological coughing, especially coughing that is associated with airway inflammation. This is because stimulation of vagal C-fibers leads to strong urge to cough sensations, and because C-fiber terminals can be strongly activated by mediators associated with airway inflammation. The most direct manner in which a given mediator can activate a C-fiber terminal is through interacting ...
Source: Pulmonary Pharmacology and Therapeutics - March 11, 2019 Category: Respiratory Medicine Source Type: research

Antitussive therapy: A role for levodropropizine
Publication date: Available online 11 March 2019Source: Pulmonary Pharmacology & TherapeuticsAuthor(s): Surinder Birring, Francesco de Blasio, Peter Dicpinigaitis, Giovanni Fontana, Luigi Lanata, Clive Page, Federico Saibene, Alessandro ZanasiAbstractCough is a protective reflex that serves to clear the airways of excessive secretions and foreign matter and which sometimes becomes excessive, and troublesome to patients. Cough is one of the most common reasons why individuals seek medical attention. A range of drugs have been developed in the past with antitussive activity and different mechanisms of action, but there a...
Source: Pulmonary Pharmacology and Therapeutics - March 11, 2019 Category: Respiratory Medicine Source Type: research

Why chronic cough in children is different
Publication date: Available online 6 March 2019Source: Pulmonary Pharmacology & TherapeuticsAuthor(s): Ahmad Kantar, Manuela SeminaraAbstractRecently, there have been robust changes in our knowledge of the neurophysiology of cough and novel clinical etiologies. Specifically, cough hypersensitivity in adults and protracted bacterial bronchitis (PBB) in children have been increasingly investigated, and differences between chronic cough in children and adults have been widely reported. In young children, postinfectious cough, bronchiectasis, airway malacia, PBB, and asthma appear to be the main causes of cough; however, b...
Source: Pulmonary Pharmacology and Therapeutics - March 6, 2019 Category: Respiratory Medicine Source Type: research

Editorial Board
Publication date: April 2019Source: Pulmonary Pharmacology & Therapeutics, Volume 55Author(s): (Source: Pulmonary Pharmacology and Therapeutics)
Source: Pulmonary Pharmacology and Therapeutics - March 6, 2019 Category: Respiratory Medicine Source Type: research

Chronic cough and obesity
Publication date: Available online 25 February 2019Source: Pulmonary Pharmacology & TherapeuticsAuthor(s): Laurent GuilleminaultAbstractWith respective prevalence of 13% and 9.6%, obesity and chronic cough are two common conditions worldwide. The crucial role of obesity has been highlighted in the development and progression of many respiratory diseases. According to the results of epidemiological studies, obesity, particularly abdominal obesity, may also be associated with chronic cough (CC). CC seems to be more severe in obese patients compared to normal-weight subjects. The management of CC may differ slightly in ob...
Source: Pulmonary Pharmacology and Therapeutics - February 26, 2019 Category: Respiratory Medicine Source Type: research

Non-pharmacological interventions for chronic cough: The past, present and future
Publication date: Available online 23 February 2019Source: Pulmonary Pharmacology & TherapeuticsAuthor(s): S. Chamberlain Mitchell, J. Ellis, S. Ludlow, A. Pandyan, S.S. BirringAbstractNon-pharmacological interventions have been explored in people with refractory chronic cough. Normally delivered by Physiotherapists and or Speech and Language Therapists, these interventions aim to educate patients about their cough, provide them with cough suppression techniques and breathing exercises, improve vocal/laryngeal hydration and psychoeducational counselling to help them gain greater control of their cough. Six key studies ...
Source: Pulmonary Pharmacology and Therapeutics - February 25, 2019 Category: Respiratory Medicine Source Type: research

Aminophylline increases parasternal muscle action in awake canines
Publication date: Available online 21 February 2019Source: Pulmonary Pharmacology & TherapeuticsAuthor(s): Jenny V. Suneby Jagers, Michael Ji, Bruce Rothwell, Paul A. EastonAbstractThe traditional theophylline bronchodilator, aminophylline, is still widely used, especially in the treatment of COPD. The effects of aminophylline on ventilation and action of the costal diaphragm have been previously defined, but other respiratory muscles – notably the chest wall, are not well determined. Therefore, we investigated the effects of aminophylline on the Parasternal intercostal, a key obligatory inspiratory muscle, exami...
Source: Pulmonary Pharmacology and Therapeutics - February 22, 2019 Category: Respiratory Medicine Source Type: research

Precision-cut lung slices from bleomycin treated animals as a model for testing potential therapies for idiopathic pulmonary fibrosis
In this study we have described precision-cut lung slices (PCLS) prepared from bleomycin treated mice as an in vitro model for testing of novel compounds with antifibrotic activity. We have shown that PCLS during in vitro incubation retain characteristics of bleomycin model with increased expression of fibrosis related genes ACTA2 (α-smooth muscle actin), COL1A1 (collagen 1), FN1 (fibronectin 1), MMP12 (matrix metalloproteinase 12) and TIMP1 (tissue inhibitor of metalloproteinases). To further evaluate PCLS as an in vitro model, we have tested ALK5 inhibitor SB525334 which was previously shown to attenuate fibrosis i...
Source: Pulmonary Pharmacology and Therapeutics - February 15, 2019 Category: Respiratory Medicine Source Type: research

Cough in exercise and athletes
Publication date: Available online 13 February 2019Source: Pulmonary Pharmacology & TherapeuticsAuthor(s): Louis-Philippe Boulet, Julie TurmelAbstractIn the general population, particularly in individuals with asthma, cough is a common symptom, often reported after exertion, although regular exercise may be associated with a reduction in the prevalence of cough. In athletes, exercise-induced cough is also a particularly frequent symptom. The main etiologies of cough in athletes are somewhat similar to non-athletes, including asthma/airway hyperresponsiveness, upper airways disorders such as allergic or non-allergic rhi...
Source: Pulmonary Pharmacology and Therapeutics - February 14, 2019 Category: Respiratory Medicine Source Type: research

Heterogeneity of cough neurobiology: Clinical implications
Publication date: Available online 11 February 2019Source: Pulmonary Pharmacology & TherapeuticsAuthor(s): Stuart B. Mazzone, Michael J. FarrellAbstractCough is an important protective mechanism for clearing the airways but becomes a troublesome, and often difficult to treat, symptom in respiratory disease. Although cough can be produced as a reflex in response to the presence of irritants within the airways, emerging research demonstrates an unappreciated complexity in the peripheral and central neural systems that regulate cough. This complexity includes multiple primary sensory neurons that can induce or facilitate ...
Source: Pulmonary Pharmacology and Therapeutics - February 12, 2019 Category: Respiratory Medicine Source Type: research

Inhalable dry powder prepared from folic acid-conjugated docetaxel liposomes alters pharmacodynamic and pharmacokinetic properties relevant to lung cancer chemotherapy
In this study, we compared the physicochemical property, anti-cancer activity, tumor targeting and pharmacokinetic behavior of docetaxel-loaded folic acid-conjugated liposomes (LPs-DTX-FA) with those of dry powder prepared by co-spray-drying LPs-DTX-FA. The particle size and PDI after re-dispersion of the powder were increased. The re-dispersed liposomes showed increased cellular uptake via micropinocytosis and exhibited higher cytotoxicity than LPs-DTX-FA. Tumor targeting of re-dispersed liposomes was less effective compared with LPs-DTX-FA but the metabolism of re-dispersed liposomes was decreased. Tracheal administratio...
Source: Pulmonary Pharmacology and Therapeutics - February 8, 2019 Category: Respiratory Medicine Source Type: research

Cough in pulmonary tuberculosis: Existing knowledge and general insights
Publication date: Available online 1 February 2019Source: Pulmonary Pharmacology & TherapeuticsAuthor(s): Richard Douglas TurnerAbstractCough is a prominent symptom of pulmonary tuberculosis (TB), one of the oldest and most prevalent infectious diseases. Coughing probably has a pivotal role in transmission of the causative organism Mycobacterium tuberculosis. Despite this, little research to date has addressed this subject. Current knowledge of the mechanisms of cough in TB and how exactly coughing patterns predict infectiousness is scant, but this is changing. This overview summarises the existing evidence for the inf...
Source: Pulmonary Pharmacology and Therapeutics - February 2, 2019 Category: Respiratory Medicine Source Type: research

SUMOylation of Vps34 by SUMO1 promotes phenotypic switching of vascular smooth muscle cells by activating autophagy in pulmonary arterial hypertension
In this study, we explored the role of SUMO1 in the dedifferentiation of vascular smooth muscle cells (VSMCs) involved in hypoxia-induced pulmonary vascular remodeling and PAH in vivo and in vitro.ResultsIn a mouse model of hypoxic PAH, SUMO1 expression was significantly increased, which was associated with activation of autophagy (increased LC3b and decreased p62), dedifferentiation of pulmonary arterial VSMCs (reduced α-SMA, SM22 and SM-MHC), and pulmonary vascular remodeling. Similar results were obtained in a MCT-induced PAH model. Overexpression of SUMO1 significantly increased VSMC proliferation, migration, hyp...
Source: Pulmonary Pharmacology and Therapeutics - January 28, 2019 Category: Respiratory Medicine Source Type: research

Adrenomedullin mediates pro-angiogenic and pro-inflammatory cytokines in asthma and COPD
ConclusionsThese data suggest that AM mediates the secretion of pro-angiogenic and pro-inflammatory cytokines in a cell-type and/or a disease-specific way, explaining its association with clinical outcomes in COPD. (Source: Pulmonary Pharmacology and Therapeutics)
Source: Pulmonary Pharmacology and Therapeutics - January 25, 2019 Category: Respiratory Medicine Source Type: research

Limitations of the results from randomized clinical trials involving intravenous and nebulised magnesium sulphate in adults with severe acute asthma
Publication date: Available online 17 January 2019Source: Pulmonary Pharmacology & TherapeuticsAuthor(s): Eugen Javor, Sanja Popović GrleAbstractThe role of intravenous (IV) or nebulised magnesium sulphate (MgSO4) in the treatment of severe acute asthma in adults is unclear. A controversy exists regarding its efficacy. In children MgSO4 has a more evident clinical effect, but the child population has not been considered in this work. The applicability of the results from randomized clinical trials (RCTs) involving MgSO4 in adult population is questioned in the optimal treatment of asthma exacerbations. According to th...
Source: Pulmonary Pharmacology and Therapeutics - January 18, 2019 Category: Respiratory Medicine Source Type: research

Vitamin D prevents experimental lung fibrosis and predicts survival in patients with idiopathic pulmonary fibrosis
Publication date: Available online 16 January 2019Source: Pulmonary Pharmacology & TherapeuticsAuthor(s): Vasilios Tzilas, Evangelos Bouros, Ilianna Barbayianni, Thodoris Karampitsakos, Sofia Kourtidou, Maria Ntassiou, Ioanna Ninou, Vassilis Aidinis, Demosthenes Bouros, Argyris TzouvelekisAbstractBackgroundVitamin D (VitD) is a steroid hormone with cytoprotective and anti-inflammatory properties. Epidemiological studies have suggested a link between VitD deficiency and risk of development of chronic lung diseases. Its role in lung fibrosis is largely unknown. The aim of our study was to investigate the role of VitD in ...
Source: Pulmonary Pharmacology and Therapeutics - January 17, 2019 Category: Respiratory Medicine Source Type: research

Editorial Board
Publication date: February 2019Source: Pulmonary Pharmacology & Therapeutics, Volume 54Author(s): (Source: Pulmonary Pharmacology and Therapeutics)
Source: Pulmonary Pharmacology and Therapeutics - January 16, 2019 Category: Respiratory Medicine Source Type: research

Alteplase and DNase for the treatment of pleural empyema in rats
ConclusionsAlteplase, DNase and alteplase + DNase changed significantly physical and chemical properties of experimental empyema at fibrinopurulent phase: alteplase reduced molecular size larger than 135 nm and DNase reduced viscosity. (Source: Pulmonary Pharmacology and Therapeutics)
Source: Pulmonary Pharmacology and Therapeutics - January 16, 2019 Category: Respiratory Medicine Source Type: research

The anti-proliferative effects of adiponectin on human lung adenocarcinoma A549 cells and oxidative stress involvement
Publication date: Available online 15 January 2019Source: Pulmonary Pharmacology & TherapeuticsAuthor(s): E. Nigro, P. Stiuso, M.G. Matera, M.L. Monaco, M. Caraglia, M. Maniscalco, F. Perrotta, G. Mazzarella, A. Daniele, A. BiancoAbstractAdiponectin (Acrp30) plays an important role in energy metabolism and inflammation. Recently, in vivo serum Acrp30 levels have been reported to be correlated to risk of developing several types of cancers such as lung cancer, and in vitro studies have demonstrated a role for Acrp30 in the control of cell proliferation and survival. However, the molecular effects of Acrp30 on lung cance...
Source: Pulmonary Pharmacology and Therapeutics - January 16, 2019 Category: Respiratory Medicine Source Type: research

Penehyclidine effects the angiogenic potential of pulmonary microvascular endothelial cells
Publication date: Available online 11 January 2019Source: Pulmonary Pharmacology & TherapeuticsAuthor(s): Peilin Xie, Zhen Zheng, Lihua Jiang, Songwei WuAbstractThe present study sought to determine the pharmacological effects of penehyclidine, an anticholinergic agent, on the angiogenic capacity of pulmonary microvascular endothelial cells (PMVECs). In vitro Matrigel network formation assay, cell proliferation assay, cell-matrix adhesion assay, and wound-healing assay were performed in PMVECs with or without exposure to penehyclidine or, in some cases, glycopyrrolate or acetylcholine, over a concentration range. In ad...
Source: Pulmonary Pharmacology and Therapeutics - January 12, 2019 Category: Respiratory Medicine Source Type: research

GYY4137 attenuates LPS-induced acute lung injury via heme oxygenase-1 modulation
This study investigated the role of GYY4137 in acute lung injury (ALI) via HO-1 regulation. Lung injury was assessed in mice challenged with intratracheal lipopolysaccharide (LPS) and the mechanism of anti-inflammatory effects of GYY4137 was investigated in mice and RAW264.7 cells. GYY4137 reduced the LPS-mediated pulmonary injury and neutrophil infiltration, and inhibited the LPS-induced production of proinflammatory cytokines, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression. Moreover, GYY4137 suppressed the LPS-evoked NF-κB activation in RAW264.7 cells. GYY4137, not time-expired G...
Source: Pulmonary Pharmacology and Therapeutics - January 1, 2019 Category: Respiratory Medicine Source Type: research

Analysis of the drop-out rate in patients receiving mepolizumab for severe asthma in real life
We describe herein the drop-out rate observed with mepolizumab in real life, because this datum can indirectly reflect the safety and tolerability aspects. The demographic and clinical data of patients receiving mepolizumab for severe asthma were collected, and the number and reasons for discontinuation of the treatment were analyzed. The database involves 143 patients (67 male, age range 19–80 year) who received at least one dose of mepolizumab. The observed discontinuation rate was 6/143 (4.2%). Five out of 6 discontinuations were due to lack of response, and one was an adverse event (urticaria) probably related to...
Source: Pulmonary Pharmacology and Therapeutics - December 29, 2018 Category: Respiratory Medicine Source Type: research

Efficacy and safety of a novel nitric oxide generator for the treatment of neonatal pulmonary hypertension: Experimental and clinical studies
Publication date: Available online 8 December 2018Source: Pulmonary Pharmacology & TherapeuticsAuthor(s): Fernanda Blasina, Lucía Vaamonde, Fernando Silvera, Gonzalo Solla, Juan Andrés Abin-Carriquiry, Carmen Gutiérrez, Pilar Beltramo, Irene García, Miguel MartellAbstractPersistent pulmonary hypertension of the newborn (PPHN) is a complex pathology resulting from a failure of the post-natal reduction in pulmonary vascular resistance leading to hypoxemia. The standard therapy is inhaled Nitric Oxide (NO) improving oxygenation but its availability is limited, especially in hospitals with restr...
Source: Pulmonary Pharmacology and Therapeutics - December 8, 2018 Category: Respiratory Medicine Source Type: research

Arbutin attenuates LPS-induced lung injury via Sirt1/ Nrf2/ NF-κBp65 pathway
Publication date: Available online 6 December 2018Source: Pulmonary Pharmacology & TherapeuticsAuthor(s): Jinyan Ye, Minqiang Guan, Yao Lu, Dan Zhang, Chengye Li, Caicun ZhouAbstractThe main goal of this study was to evaluate the effects of arbutin (AR) on lipopolysaccharide (LPS)-induced lung injury. A lung injury rat model was established by intravenous LPS administration. We found that levels of inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6) in both serum and lung tissue were significant increased after LPS challenge. In addition...
Source: Pulmonary Pharmacology and Therapeutics - December 6, 2018 Category: Respiratory Medicine Source Type: research