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RESPIRATORY DISEASES (103 journals)                     

Showing 1 - 104 of 104 Journals sorted alphabetically
Advances in Respiratory Medicine     Open Access   (Followers: 7)
Advances in Thoracic Diseases     Open Access  
American Journal of Respiratory and Critical Care Medicine     Full-text available via subscription   (Followers: 257)
American Journal of Respiratory Cell and Molecular Biology     Full-text available via subscription   (Followers: 20)
American Review of Respiratory Disease     Full-text available via subscription   (Followers: 4)
Angiologia e Cirurgia Vascular     Open Access   (Followers: 1)
Annals of the American Thoracic Society     Full-text available via subscription   (Followers: 17)
Annals of Thoracic Medicine     Open Access   (Followers: 6)
Archives of Pulmonology and Respiratory Care     Open Access   (Followers: 1)
Archivos de Bronconeumología     Full-text available via subscription  
Archivos de Bronconeumología (English Edition)     Full-text available via subscription   (Followers: 1)
Asthma Research and Practice     Open Access   (Followers: 2)
BMC Pulmonary Medicine     Open Access   (Followers: 5)
BMJ Open Respiratory Research     Open Access   (Followers: 7)
Breathe     Open Access   (Followers: 5)
Canadian Journal of Respiratory, Critical Care, and Sleep Medicine     Hybrid Journal   (Followers: 1)
Canadian Respiratory Journal     Open Access   (Followers: 3)
Case Reports in Pulmonology     Open Access   (Followers: 3)
Chest     Full-text available via subscription   (Followers: 102)
Chest Disease Reports     Open Access   (Followers: 2)
Chronic Respiratory Disease     Hybrid Journal   (Followers: 9)
Clinical Lung Cancer     Hybrid Journal   (Followers: 6)
Clinical Medicine Insights : Circulatory, Respiratory and Pulmonary Medicine     Open Access   (Followers: 3)
Clinical Pulmonary Medicine     Hybrid Journal   (Followers: 2)
COPD Research and Practice     Open Access   (Followers: 1)
COPD: Journal of Chronic Obstructive Pulmonary Disease     Hybrid Journal   (Followers: 16)
Current Opinion in Pulmonary Medicine     Hybrid Journal   (Followers: 10)
Current Pulmonology Reports     Hybrid Journal  
Current Research in Tuberculosis     Open Access   (Followers: 3)
Current Respiratory Care Reports     Hybrid Journal   (Followers: 2)
Current Respiratory Medicine Reviews     Hybrid Journal   (Followers: 5)
Der Pneumologe     Hybrid Journal   (Followers: 1)
Egyptian Journal of Chest Diseases and Tuberculosis     Open Access   (Followers: 3)
ERJ Open Research     Open Access   (Followers: 3)
Eurasian Journal of Pulmonology     Open Access  
European Clinical Respiratory Journal     Open Access   (Followers: 4)
European Respiratory Journal     Full-text available via subscription   (Followers: 39)
European Respiratory Review     Open Access   (Followers: 7)
Experimental Lung Research     Hybrid Journal   (Followers: 1)
Expert Review of Respiratory Medicine     Hybrid Journal   (Followers: 5)
Heart & Lung: The Journal of Acute and Critical Care     Hybrid Journal   (Followers: 14)
Heart, Lung and Circulation     Full-text available via subscription   (Followers: 9)
Indian Journal of Respiratory Care     Open Access   (Followers: 3)
Indian Journal of Tuberculosis     Full-text available via subscription  
Influenza and Other Respiratory Viruses     Open Access   (Followers: 3)
International Journal of Chronic Obstructive Pulmonary Disease     Open Access   (Followers: 3)
Journal of Association of Chest Physicians     Open Access   (Followers: 2)
Journal of Asthma     Hybrid Journal   (Followers: 5)
Journal of Asthma Allergy Educators     Hybrid Journal   (Followers: 5)
Journal of Bronchology & Interventional Pulmonology     Hybrid Journal   (Followers: 5)
Journal of Clinical Tuberculosis and Other Mycobacterial Diseases     Open Access  
Journal of Heart and Lung Transplantation     Hybrid Journal   (Followers: 12)
Journal of Respiratory Medicine     Open Access   (Followers: 5)
Journal of Respiratory Research     Open Access   (Followers: 2)
Journal of Tuberculosis Research     Open Access   (Followers: 1)
Jurnal Respirasi     Open Access  
Karger Kompass Pneumologie     Full-text available via subscription   (Followers: 1)
Kindheit und Entwicklung     Hybrid Journal  
Lung     Hybrid Journal   (Followers: 3)
Lung Cancer     Hybrid Journal   (Followers: 16)
Lung Cancer International     Open Access   (Followers: 2)
Lung Cancer: Targets and Therapy     Open Access   (Followers: 3)
Lung India     Open Access   (Followers: 1)
Multidisciplinary Respiratory Medicine     Open Access   (Followers: 4)
npj Primary Care Respiratory Medicine     Open Access   (Followers: 2)
Open Journal of Respiratory Diseases     Open Access   (Followers: 2)
Open Respiratory Medicine Journal     Open Access   (Followers: 2)
Paediatric Respiratory Reviews     Hybrid Journal   (Followers: 11)
Pediatric Quality & Safety     Open Access  
Pediatric Respirology and Critical Care Medicine     Open Access   (Followers: 1)
Pulmonary Circulation     Open Access   (Followers: 4)
Pulmonary Medicine     Open Access   (Followers: 3)
Pulmonary Pharmacology & Therapeutics     Hybrid Journal   (Followers: 2)
Pulmonary Therapy     Open Access   (Followers: 2)
Pulmonology and Respiratory Research     Open Access   (Followers: 2)
Respiratory Care     Full-text available via subscription   (Followers: 11)
Respiratory Investigation     Full-text available via subscription   (Followers: 1)
Respiratory Medicine     Hybrid Journal   (Followers: 18)
Respiratory Medicine : X     Open Access  
Respiratory Medicine Case Reports     Open Access  
Respiratory Medicine CME     Hybrid Journal  
Respiratory Medicine Extra     Full-text available via subscription   (Followers: 1)
Respiratory Physiology & Neurobiology     Hybrid Journal   (Followers: 4)
Respiratory Research     Open Access   (Followers: 1)
Respirology     Hybrid Journal   (Followers: 5)
Respirology Case Reports     Open Access  
Revista Americana de Medicina Respiratoria     Open Access  
Revista Chilena de Enfermedades Respiratorias     Open Access  
Revista Inspirar     Open Access  
Revista ORL     Open Access  
Revista Portuguesa de Pneumologia     Open Access  
Sarcoidosis Vasculitis and Diffuse Lung Disese     Full-text available via subscription   (Followers: 3)
Seminars in Respiratory and Critical Care Medicine     Hybrid Journal   (Followers: 14)
Sleep Medicine Reviews     Hybrid Journal   (Followers: 17)
The Clinical Respiratory Journal     Hybrid Journal   (Followers: 3)
The International Journal of Tuberculosis and Lung Disease     Full-text available via subscription   (Followers: 8)
The Lancet Respiratory Medicine     Full-text available via subscription   (Followers: 35)
Therapeutic Advances in Chronic Disease     Open Access   (Followers: 7)
Therapeutic Advances in Respiratory Disease     Open Access   (Followers: 1)
Thorax     Hybrid Journal   (Followers: 38)
Translational Respiratory Medicine     Open Access   (Followers: 1)
Tuberculosis     Hybrid Journal   (Followers: 12)
Tuberculosis Research and Treatment     Open Access   (Followers: 3)
Пульмонология     Full-text available via subscription  

           

Similar Journals
Journal Cover
Pulmonary Pharmacology & Therapeutics
Journal Prestige (SJR): 0.86
Citation Impact (citeScore): 2
Number of Followers: 2  
 
  Hybrid Journal Hybrid journal (It can contain Open Access articles)
ISSN (Print) 1094-5539 - ISSN (Online) 1522-9629
Published by Elsevier Homepage  [3203 journals]
  • Tolerability of nintedanib-related diarrhea in patients with idiopathic
           pulmonary fibrosis
    • Abstract: Publication date: Available online 20 March 2020Source: Pulmonary Pharmacology & TherapeuticsAuthor(s): Yasutaka Hirasawa, Mitsuhiro Abe, Jiro Terada, Masashi Sakayori, Kenichi Suzuki, Keiichiro Yoshioka, Takeshi Kawasaki, Kenji Tsushima, Koichiro Tatsumi
       
  • JMV5656, a short synthetic derivative of TLQP-21, alleviates acid-induced
           lung injury and fibrosis in mice
    • Abstract: Publication date: Available online 20 March 2020Source: Pulmonary Pharmacology & TherapeuticsAuthor(s): Vanessa Zambelli, Laura Rizzi, Paolo Delvecchio, Elena Bresciani, Laura Molteni, Ramona Meanti, Verdiè Pascal, Jean-Alain Fehrentz, Robert J. Omeljaniuk, Giacomo Bellani, Antonio Torsello
       
  • The role of increased red cell distribution width as a negative prognostic
           marker in patients with COPD
    • Abstract: Publication date: February 2020Source: Pulmonary Pharmacology & Therapeutics, Volume 60Author(s): Theodoros Karampitsakos, Katerina Dimakou, Ourania Papaioannou, Serafeim Chrysikos, Maria Kaponi, Demosthenes Bouros, Argyrios Tzouvelekis, Georgios Hillas
       
  • Biologics and Bronchial Thermoplasty for severe refractory asthma
           treatment: From eligibility criteria to real practice. A cross-sectional
           study
    • Abstract: Publication date: February 2020Source: Pulmonary Pharmacology & Therapeutics, Volume 60Author(s): Francesco Menzella, Carla Galeone, Patrizia Ruggiero, Diego Bagnasco, Chiara Catellani, Nicola Facciolongo
       
  • Lung cancer in patients with Idiopathic Pulmonary Fibrosis. A
           retrospective multicenter study in Greece
    • Abstract: Publication date: February 2020Source: Pulmonary Pharmacology & Therapeutics, Volume 60Author(s): Argyris Tzouvelekis, Theodoros Karampitsakos, Georgia Gomatou, Evangelos Bouros, Vassilios Tzilas, Efrossyni Manali, Ioannis Tomos, Athina Trachalaki, Lykourgos Kolilekas, Ioanna Korbila, Periklis Tomos, Serafeim Chrysikos, Mina Gaga, Zoe Daniil, Fotini Bardaka, Ilias C. Papanikolaou, Christopher Euthymiou, Despoina Papakosta, Paschalis Steiropoulos, Paschalis Ntolios
       
  • Open triple therapy for chronic obstructive pulmonary disease: Patterns of
           prescription, exacerbations and healthcare costs from a large Italian
           claims database
    • Abstract: Publication date: Available online 21 February 2020Source: Pulmonary Pharmacology & TherapeuticsAuthor(s): Silvia Calabria, Giulia Ronconi, Letizia Dondi, Carlo Piccinni, Antonella Pedrini, Immacolata Esposito, Riccardo Pistelli, Nello MartiniAbstractBackgroundThe combination of two long acting bronchodilators with an inhaled corticosteroid, known as Triple Therapy (TT), is a usual clinical practice for patients affected by chronic obstructive pulmonary disease (COPD). This analysis aimed to identify subjects with COPD treated with extemporaneous combination of ICS/LABA and LAMA (namely open TT) and to describe the pharmacological strategy, the spirometry use, the exacerbations occurrence and the costs, in the perspective of the Italian National Health System (NHS).MethodsThrough record linkage of administrative data (ReS database) of about 12 million inhabitants in 2014, a cohort of patients aged ≥45, without asthma and treated with open TT (index date) was selected. Specific drugs, oxygen supply and exacerbations were described in one year before the index date, while spirometry tests over two years before the index date. All these resources utilization, the persistence to the open TT, and integrated costs of the above healthcare services were analysed for 1-year follow-up.ResultsIn 2014, 10,352 patients (mean age 74 ± 9; males 66.0%) with COPD and treated with open TT were identified (prevalence 160.6 per 100,000 inhabitants aged ≥45). During the previous year, the 44.0% of this cohort was already treated with open TT, 7.0% did not received any drugs for obstructive airway diseases, 11.1% needed home oxygen therapy, and 28.7% experienced at least an exacerbation. In the follow-up year, the 37.5% of the cohort was found persistent to the open TT, 17.0% needed oxygen therapy, and the 30.9% underwent an exacerbation. Spirometry was performed on 45.7% of patients in the two previous years, while on 33.3% in the subsequent year. In the follow-up, on average, every patient of the cohort costed to the NHS €5,295: 48.2% for hospitalizations, 41.2% for drugs and 10.6% for outpatient services.ConclusionsThis large observational study based on claims data reliably identified subjects with COPD treated with open TT and their burden on the NHS. Moreover, it could describe the real clinical management of the open TT, before the marketing of the fixed one. These findings are useful for health policymakers in order to promote the appropriate utilization of both currently marketed and future therapies.
       
  • Determinants of response to bronchodilator in patients with cough variant
           asthma- A randomized, single-blinded, placebo-controlled study
    • Abstract: Publication date: Available online 21 February 2020Source: Pulmonary Pharmacology & TherapeuticsAuthor(s): Fang Yi, Lina Han, Baojuan Liu, Xu Zhang, Yongxin Xue, Wei Luo, Qiaoli Chen, Kefang LaiAbstractBackgroundNot all patients with cough variant asthma (CVA) show responsiveness to bronchodilators (RB) in clinic. Whether there are specific clinical and pathophysiological features can indicate RB in patients with CVA needs further investigation. Thus, we aimed to investigate the RB in patients with CVA and associated factors.MethodsForty-two CVA patients were randomized in a 2:1 ratio to receive oral bambuterol hydrochloride (10 mg, once daily, for 3 days) or matched placebo, 36 patients (24 with bronchodilator and 12 with placebo) completed the study eventually. RB was considered when cough visual analogue scale (VAS) score decreased 30% or more after 3 days treatment. The baseline clinical and pathophysiological characteristics between patients with RB and patients without RB were compared. CRS was presented with the lowest concentration of capsaicin inducing at least 5 coughing (C5).ResultsThe responsive rate of patients with bronchodilator was significantly higher than that with placebo (62.5% vs 16.7%, p 
       
  • Bioequivalence studies of inhaled indacaterol maleate in healthy Chinese
           volunteers under gastrointestinal non-blocking or blocking with
           concomitant charcoal administration
    • Abstract: Publication date: Available online 8 February 2020Source: Pulmonary Pharmacology & TherapeuticsAuthor(s): Chan Zou, Qian Yang, Shuang Yang, Xingfei Zhang, Xiaoyan Yang, Zhijun Huang, Qi Pei, Jie Huang, Guoping YangAbstractBackgroundIndacaterol is one of the long-acting beta2-adrenergic agonists, referred as first-line monotherapy for Chronic obstructive pulmonary disease since 2011. Generic products are encouraged to benefit the large COPD patients in China, in which can provide more choices association with reduced cost and improve the quality of patient life.ObjectiveThe three-part study consists of two independent cohorts of thirty-six subjects, aimed to evaluate the bioequivalence (BE) of two indacaterol formulations in gastrointestinal (GI) absorption charcoal-block or non-block conditions. One pilot study performed in six healthy subjects to determine the blocking effect of a new charcoal-based regimen on GI absorption after orally inhalation of indacaterol.MethodsTwo BE studies were conducted with a randomized, open-label, 2-period crossover design in two independent 36-healthy-subject cohorts, equivalence in systemic and lung deposition was assessed after inhalation of a single dose of 150 μg indacaterol (test or reference formulation) alone or concomitant administration of charcoal. The charcoal-based regimen was improved by optimizing the dose and number of doses, and its blocking efficacy against GI absorption was assessed in a pilot study. Six healthy subjects received 9 g charcoal 10 min before, immediately after and 2 h after indacaterol (3 g/100 ml water × 3 times). Blood collected at predetermined time points up to 72 h. Plasma indacaterol concentrations were determined using HPLC-MS/MS. Pharmacokinetics parameters were calculated with non-compartment analysis. Equivalences were concluded if the 90% confidence interval (CI) for test: reference of Cmax and AUC0-t fell within the limits of 0.8–1.25.ResultsIndacaterol was undetectable in plasma samples in pilot study. The T/R ratio of the geometric mean Cmax and AUC0-t was 109.9% (90% CI, 106.1–113.8%) and 104.8% (90% CI, 101.5–108.1%) for charcoal-block subjects and 105.4% (90% CI, 99.8% ∼ 111.3%), and 101.0% (90% CI, 97.7%–104.4%) for non-block subjects. No serious adverse events were reported.ConclusionsThe results showed that 150 μg indacaterol (+/− 9 g charcoal) was well tolerated in all subjects. The two formulations are bioequivalent in terms of the rate and absorption both in charcoal-block and non-block conditions. The improved charcoal-based regimen demonstrated to be effective and fully blockade of GI absorption of indacaterol.
       
  • Hypertonic saline reduces cell infiltration into the lungs after brain
           death in rats
    • Abstract: Publication date: Available online 7 February 2020Source: Pulmonary Pharmacology & TherapeuticsAuthor(s): Cristiano de Jesus Correia, Raphael dos Santos Coutinho e Silva, Rafaela Garcia Ferreira Soares, Roberto Armstrong, Fernanda Yamamoto Ricardo-da-Silva, Paulina Sannomiya, Ana Cristina Breithaupt-Faloppa, Luiz Felipe P. MoreiraAbstractBackgroundLung transplantation is a treatment method for end stage lung disease, but the availability of donor lungs remains a major constraint. Brain death (BD) induces hemodynamic instability with microcirculatory hypoperfusion and increased inflammation, leading to pulmonary dysfunction. Hypertonic saline solution (HSS) is a volume expander possessing immunomodulatory effects. This study evaluated the influence of HSS on pulmonary dysfunction and inflammation in a rat model of BD.MethodsBD was induced by inflation of an intracranial balloon catheter. Rats were divided into [1]: Sham, without BD [2]; NS, NaCl treatment (0.9%, 4 mL/kg, i.v.) immediately after BD [3]; HSS1, HSS treatment (NaCl 7.5%, 4 mL/kg, i.v.) immediately after BD; and [4] HSS60, HSS treatment 60 min post BD. All groups were analyzed after 360 min.ResultsAnimals subjected to BD exhibited increased exhaled O2 and decreased CO2.The number of leukocytes in the lungs was significantly increased in the NS group (p = 0.002) and the HSS treatment was able to reduce it (HSS1, p = 0.018 and HSS60 = 0.030). In parallel, HSS-treated rats showed reduced levels of ICAM-1 expression, which was increased in the NS respective to Sham group. Lung edema was found increased in the NS group animals compared to Sham and no effect of the HSS treatment was observed. There were no differences among the groups in terms of TNF-α, VEGF, and CINC-1 lung concentrations.ConclusionsHSS is capable of reducing inflammatory cell infiltration into the lung after BD induction, which is associated with the reduction of ICAM-1 expression in organ vessels.
       
  • Asthmatic children and MDI verbal inhalation technique counseling
    • Abstract: Publication date: Available online 24 January 2020Source: Pulmonary Pharmacology & TherapeuticsAuthor(s): Marwa O. Elgendy, Amany H. Hassan, Haitham Saeed, Mohamed E. Abdelrahim, Randa Salah EldinObjectivesThe present work aimed to study the role of metered-dose inhalers (MDI) verbal counseling on asthmatic children patients inhalation technique and their pulmonary functions.MethodsIn this study many children younger than 18 years old with asthma were collected from University hospital outpatient clinics throughout two years period Their MDI inhalation technique was checked and the number of MDI inhalation technique mistakes were detected and corrected at the first visit and every month for two more visits (three visits). Their peak expiratory flow (PEF) and forced expiratory volume in 1 s (FEV1) as a percentage of the forced vital capacity (FVC) were checked at every visit.Results81 asthmatic subjects (54 female) younger than 18 years old were collected with a mean (SD) age 14.4 (1.8) years old. Most of the patients' owned MDI contained salbutamol, however, some patients were using Beclometasone MDI or Beclometasone and salbutamol combination MDI. The mean number of correct steps performed was significantly increased (p 
       
  • Effect of piperlongumine during exposure to cigarette smoke reduces
           inflammation and lung injury
    • Abstract: Publication date: Available online 24 January 2020Source: Pulmonary Pharmacology & TherapeuticsAuthor(s): Monielle Sant’Ana Leal, Helena R. Souza, Lucas Possebon, Marinônio L. Cornélio, Yanira Riffo-Vasquez, Ana Paula Girol, Sonia M. OlianiChronic obstructive pulmonary disease (COPD) is related to smoking and anti-inflammatory therapy is indicated. Among the mediators with anti-inflammatory properties, we highlight piperlongumine (PL), an alkaloid/amide of Piper longum. Here we evaluated the PL administration on an experimental model of respiratory inflammation resulting from exposure to cigarette smoke. Male Balb/c mice were exposed to burning of 10 commercial cigarettes, 2x/day, for five weeks on specific equipment. PL efficacy was evaluated in control, exposed to smoke without treatment and PL treated (2.0 mg/kg, 3x/week) groups. Animals were weighed and plethysmographic analyses performed at the end of the exposure protocol. Inflammatory cells were evaluated in the bronchoalveolar lavage (BAL) and hemoglobin and glucose in the blood. Lung fragments were processed for histopathological studies and AnxA1, COX-2, NF-kB and neutrophil elastase expressions. Plethysmography revealed that PL maintained pulmonary frequency, volume and ventilation parameters similar to controls, with respiratory volume reduction compared to untreated animals. Final weight was reduced in both exposed groups. PL decreased hemoglobin concentration, attenuated the reduction of glucose levels and reduced influx of lymphocytes, neutrophils and macrophages in BAL. Histopathologically occured infiltration of inflammatory cells, increase of the interalveolar septa and intra-alveolar spaces in untreated animals. But, PL administration recovered lung tissues and, immunohistochemically, promoted increased expression of AnxA1 and reduction of COX-2, NF-kB and neutrophil elastase. Together the results indicate that PL attenuates systemic and pulmonary inflammatory changes, partially by modulating the expression the endogenous AnxA1, and may represent a promising therapy in preventing the inflammation induced by cigarette smoke.Graphical abstractImage 1
       
  • Dual use of bronchodilators versus monotherapy, and its impact on
           pulmonary rehabilitation in COPD patients
    • Abstract: Publication date: Available online 21 January 2020Source: Pulmonary Pharmacology & TherapeuticsAuthor(s): Vicente Benavides-Cordoba, Sebastian Aviles, Camila Ascuntar, Lina Orozco, Ricardo Mosquera, Julian RiveraAbstractIntroductionLong-acting bronchodilators are the therapy with the best evidence for treating stable chronic obstructive pulmonary disease (COPD). Long-acting combinations of β2 agonists and anticholinergics (LABA-LAMA) are recommended in advanced stages when monotherapy has not generated the desired effects. Pulmonary Rehabilitation (PR) is an effective non-pharmacological strategy. The aim of this study was to compare the results obtained in patients with COPD who received monotherapy versus dual bronchodilator therapy in terms of functional aerobic capacity, symptoms and quality of life.Materials and methodsProspective non randomized intervention study; the patients were divided into two groups: in one group patients were treated with LAMA (Tiotropium Bromide, 5 μg every 24 h) and in the other group patients were treated with LABA + LAMA (Indacaterol/Glycopyrronium, 110/50 μg once a day). After receiving the concept of pulmonology, patients were intervened with 8 weeks of PR. The study was approved by the committee of the Clinica Neumológica del Pacifico in Cali and the Institución Universitaria Escuela Nacional del Deporte, Colombia. To determine the differences, t pair test for intragroup, and t-test was performed for intergroup analysis. For all tests, a p-value
       
  • Mepolizumab effectiveness on small airway obstruction, corticosteroid
           sparing and maintenance therapy step-down in real life
    • Abstract: Publication date: Available online 21 January 2020Source: Pulmonary Pharmacology & TherapeuticsAuthor(s): Sposato Bruno, Camiciottoli Gianna, Bacci Elena, Scalese Marco, Carpagnano Giovanna Elisiana, Pelaia Corrado, Santus Pierachille, Maniscalco Mauro, Masieri Simonetta, Angelo Corsico, Nicola Scichilone, Baglioni Stefano, Murgia Nicola, Folletti Ilenia, Bardi Giulio, Grosso Amelia, Cameli Paolo, Latorre Manuela, Antonino Musarra, Bargagli ElenaAbstractBackgroundMepolizumab (MEP) has been recently introduced to treat severe eosinophilic asthma. Trials have demonstrated a significant effectiveness in this phenotype. We evaluated MEP efficacy on lung function, symptoms, asthma exacerbations, biologic markers, steroid dependence and controller treatment level in real-life.MethodsWe retrospectively analyzed 134 severe asthmatics (61 males; mean age 58.3 ± 11; mean FEV1%:72 ± 21), treated with MEP for at least 6 months (mean duration:10.9 ± 3.7 months).ResultsFEV1% improved significantly after MEP. Mean FEF25-75 also increased from 37.4 ± 25.4% to 47.2 ± 27.2% (p 
       
  • Presence and function of β-adrenergic receptors in primary equine
           bronchial epithelia cells
    • Abstract: Publication date: Available online 18 January 2020Source: Pulmonary Pharmacology & TherapeuticsAuthor(s): Linda Marie Schellenberg, Jana Bonicelli, Ina Hochheim, Ralf Regenthal, Getu AbrahamAbstractThe β-adrenergic receptor (β-AR) plays an important role in regulating a variety of cell and organ functions in different animal species and is an important target in asthma pathogenesis and therapy. The β-AR expression and function in equine bronchial epithelial cells (EBEC) were not known but innervation and significant decrease in receptor level were reported in the equine bronchial tissues from asthmatic horses. 125I-iodocyanopindolol (ICYP) binding studies were undertaken in primary freshly isolated and cultured EBEC to identify the presence of the β-ARs. The receptor distribution was assessed using subtype-selective β-AR antagonists (ICI 118 551 (β2) and CGP 20712A (β1). The β-AR function was confirmed by measuring the agonist-induced intracellular cAMP accumulation in freshly isolated and cultured EBEC. In both freshly isolated and cultured EBEC, the specific ICYP binding was saturable and of high affinity. The maximal receptor density (Bmax) was 9763 ± 140 binding sites/cell (mean ± SEM, n = 7) and 10575 ± 194 binding sites/cell (mean ± SEM, n = 5) in freshly isolated and cultured EBEC, respectively. The receptor affinity to the ligand (KD) was also not different between the two cell conditions. ICI 118.551 displaced ICYP with 25 000-fold higher affinity than CGP 20712A. Moreover, in both fresh isolated and cultured EBEC, cAMP-accumulation was stimulated with a rank-order of potency of isoproterenol > adrenaline > noradrenaline. These results highlight the β2-AR to be a key subtype in both freshly isolated and cultured primary EBEC.
       
  • Eucalyptol reduces airway hyperresponsiveness in rats following cigarette
           smoke-exposed
    • Abstract: Publication date: April 2020Source: Pulmonary Pharmacology & Therapeutics, Volume 61Author(s): Emanuel Kennedy-Feitosa, Paolo Oliveira-Melo, Eder Evangelista-Costa, Daniel Silveira Serra, Francisco Sales Ávila Cavalcante, Edson Lopes da Ponte, Roseli Barbosa, Renata Evangelista Rodrigues da Silva, Ana Maria Sampaio Assreuy, José Henrique Leal-Cardoso, Crystianne Calado LimaAbstractBackgroundCigarette smoke is the major cause of airway inflammatory disease, including airway hyperresponsiveness. Eucalyptol (EUC), also named 1.8-cineole, is a monoterpenoid found in essential oil of medicinal plants, showing several biological effects.Hypothesis/purposeBased in the eucalyptol protective activity in respiratory diseases as asthma, our hypothesis is that eucalyptol is able to reduce the airway hyperresponsiveness and the respiratory mechanic parameters in rats exposed to cigarette smoke.Study designWistar rats were divided into control and cigarettes smoke (CS) groups. CS group was daily subjected to cigarette smoke and treated by inhalation for 15 min/day with EUC (1 mg/mL) or vehicle during 30 days. After treatment, bronchoalveolar lavage (BAL) was collected to analyze the inflammatory profile, and tracheal rings were isolated for evaluation of the airway smooth muscle hyperresponsiveness. Lung function was analyzed in vivo.MethodsThe inflammatory profile was evaluated by optical microscopy performing total (Neubauer chamber) and differential leukocyte count (smear slides stained in H&E). The hyperresponsiveness was evaluated in tracheal rings contracted with potassium chloride (KCl) carbamoylcholine (CCh), or Barium chloride (BaCl2) in presence or absence of nifedipine. The lung function (Newtonian resistance-RN) was evaluated by bronco stimulation with methacholine (MCh).ResultsBAL from CS group increased the influx of leukocyte, mainly neutrophils and macrophages compared to control group. EUC reduced by 71% this influx. The tracheal contractions induced by KCl, CCh or BaCl2 were reduced by EUC in 59%, 42% and 26%, respectively. The last one was not different of nifedipine activity. Newtonian resistance (RN) was also reduced in 37% by EUC compared to CS group. 
ConclusionEUC reduces the hyperresponsiveness and the airway inflammatory profile, recovering the lung function.
       
  • Multiple single nucleotide polymorphisms of the transient receptor
           potential vanilloid 1 (TRPV1) genes associate with cough sensitivity to
           capsaicin in healthy subjects
    • Abstract: Publication date: Available online 11 January 2020Source: Pulmonary Pharmacology & TherapeuticsAuthor(s): Filippo Liviero, Manuela Campisi, Maria C. Scarpa, Paola Mason, Gabriella Guarnieri, Piero Maestrelli, Sofia PavanelloAbstractBackgroundCough is a common symptom in several respiratory diseases and may occur in healthy subjects as a defense mechanism against noxious inhalants. Cough response is mediated by transient receptor potential vanilloid-1 (TRPV1) expressed by C-fibers in the airways. Capsaicin (CPS) activates TRPV1 and is regularly used as a tool to study cough response. Although single nucleotide polymorphisms (SNPs) of TRPV1 are implicated in CPS binding, their role in cough response is not fully elucidated.AimsIn this study we investigated the relationship between capsaicin cough challenge sensitivity and multiple TRPV1 polymorphisms.MethodsThe dose-response of cough induced by CPS inhalation was determined in 20 unselected healthy volunteers and the concentration of CPS causing two coughs (C2) was calculated. The SNPs I585V(rs8065080), T505A(rs17633288), T469I(rs224534), I315 M(rs222747), P91S(rs222749), and K2N(rs9894618) were characterized in blood DNA from each subject. The association between combinations of TRPV1 SNPs and CPS sensitivity of each subject was assessed by linear regression.ResultsAll subjects were wild type for T505A and K2N, while they exhibited two to six SNPs with high capsaicin responsiveness. The major contribution to CPS sensitivity in vivo (C2) was due to four combined SNPs: 315 M, 585I, 469I and 91S (p = 0.015). We found, however, that the presence of a minimum of two polymorphisms, such as 91S combined with 315 M (p = 0.032) or 91S with 585I (p = 0.025), was sufficient to detect an effect on C2.ConclusionCapsaicin cough challenge sensitivity in healthy subjects is dependent on multiple TRPV1 polymorphisms.
       
  • Contribution of angiotensin II in hepatic ischemia /reperfusion induced
           lung injury: Acute versus chronic usage of captopril
    • Abstract: Publication date: February 2020Source: Pulmonary Pharmacology & Therapeutics, Volume 60Author(s): Laila Ahmed El-sayed, Eman Osama, Marwa Nagi Mehesen, Laila Ahmed Rashed, Alshaymaa Gamal Aboulkhair, Abeer Ibraheem Omar, Asmaa Mohammed Shams EldeenBackgroundAcute lung injury is one of the most popular consequences of hepatic ischemia/reperfusion (I/R) injury. Recently it was documented that renin-angiotensin system plays a key role in tissue inflammation, generation of reactive oxygen species (ROS) and tumor necrosis factor-alpha (TNF-α) (the principal liver injury mediators) during I/R.Material and methodsWe investigated the effect of acute versus chronic usage of angiotensin converting enzyme inhibitor (captopril) on liver inflammation and lung injury caused by hepatic ischemia for 1h followed by 24h reperfusion. Forty adult Wistar male rats were divided into sham, I/R, I/R-acute captopril (100 mg/kg, 24 and 1.5 h before surgery) and I/R-chronic captopril (10 mg/kg/day for 28 days before surgery) groups.ResultsWe found captopril pretreatment significantly decreased liver damage indices, adhesion molecules, and TNF-α level in hepatic and tracheal tissues. Histologically, acute captopril pretreatment significantly decreased hepatic Kupffer cells number and lung α-smooth muscle actin expression more than chronic pretreatment. Increased tracheal tone, in response to acetylcholine, was suppressed by acute and chronic captopril pretreatment.ConclusionAngiotensin II plays a key role in tissue inflammation and airway hyperresponsiveness (AHR) via enhancing production of TNF-α. With more protection observed in lung, acute captopril could attenuate liver-induced lung injury via lowering TNF-α; a suggested possible mediator of airway hyperreactivity.Graphical abstractImage 1
       
  • A long-term clinical trial on the efficacy and safety profile of
           doxofylline in Asthma: The LESDA study
    • Abstract: Publication date: February 2020Source: Pulmonary Pharmacology & Therapeutics, Volume 60Author(s): Luigino Calzetta, Maria Gabriella Matera, Marc F. Goldstein, William R. Fairweather, William W. Howard, Mario Cazzola, Paola RoglianiAbstractDoxofylline, an oral methylxanthine with bronchodilator and anti-inflammatory activities, offers a promising alternative to theophylline due to its superior efficacy/safety profile. No long-term studies on the efficacy and safety of doxofylline are currently available in asthma. The aim of the Long-term clinical trial on the Efficacy and Safety profile of Doxofylline in Asthma (LESDA) study was to investigate the safety and efficacy profile of doxofylline administered for one year in asthmatic patients. LESDA was a multicenter, open-label, Phase III, clinical trial in which adult asthmatic patients received the same treatment (oral doxofylline 400 mg t.i.d.) for one year. Efficacy was assessed through periodic pulmonary function tests and by having the subjects keep monthly records of asthma events rates and use of salbutamol as rescue medication. The rate of adverse events (AEs) was recorded during the study.Three-hundred nine patients were screened and allocated in the study. Doxofylline significantly improved the change from baseline in forced expiratory volume in 1 s (FEV1) (+16.90 ± 1.81%, P 
       
  • Efficacy of once-daily tiotropium Respimat in adults with asthma at GINA
           Steps 2–5
    • Abstract: Publication date: February 2020Source: Pulmonary Pharmacology & Therapeutics, Volume 60Author(s): Roland Buhl, J.M. FitzGerald, Eli O. Meltzer, Alberto de la Hoz, Ralf Sigmund, Huib A.M. Kerstjens, Eugene R. BleeckerTiotropium Respimat is an efficacious add-on to maintenance treatment in patients with symptomatic asthma. Currently, the Global Initiative for Asthma (GINA) strategy recommends tiotropium for patients at Steps 4–5. To assess the clinical benefits of tiotropium Respimat across asthma severities, GINA Steps 2–5, a post hoc analysis of five double-blind trials (12–48-weeks; patients aged 18–75 years) investigated the effect of tiotropium Respimat, 5 μg or 2.5 μg, versus placebo, on peak forced expiratory volume in 1 s (FEV1) within 3 h post-dose (FEV1(0–3h)) response, and Asthma Control Questionnaire-7 (ACQ-7) responder rate. GINA step grouping was based on patients’ background treatment regimen. Baseline characteristics of patients (N = 2926) were balanced between treatments. Tiotropium Respimat showed consistent improvements in lung function across GINA steps; placebo-corrected peak FEV1(0–3h) improvements after tiotropium Respimat 5 μg and 2.5 μg were: Step 2 (Week 8), 135 mL (95% confidence interval: 84, 187) and 155 mL (103, 206); Step 3 (Week 24), 187 mL (139, 235) and 235 mL (187, 283); Step 4 (Week 24), 111 mL (63, 159) and 181 mL (35, 326); Step 5 (Week 24; 5 μg only), 164 mL (5, 323). Asthma control improved with tiotropium Respimat versus placebo, showing statistical significance (nominal P value) with tiotropium Respimat 5 μg at Step 4 (odds ratio 1.36 [1.03, 1.78]). Safety profiles were similar between treatments. In conclusion, tiotropium Respimat add-on therapy improves lung function, and may improve asthma control, in adults across disease severities.Graphical abstractImage 1
       
  • Zileuton use and phenotypic features in asthma
    • Abstract: Publication date: February 2020Source: Pulmonary Pharmacology & Therapeutics, Volume 60Author(s): P. Thalanayar Muthukrishnan, M. Nouraie, A. Parikh, F. HolguinAbstractZileuton, a 5-lipoxygenase (5LPO) inhibitor exerts a broad influence in the arachidonic acid (AA) pathway by blocking upstream molecules that otherwise would lead to production of an array of inflammatory leukotrienes (LT) A4-E4. Hence, it has the potential to be a drug suitable to treat complicated asthmatics. Studies have shown modest response rates for zileuton in asthmatics.ObjectiveWe sought to study our hypothesis that response to zileuton varies across specific asthmatic phenotypes.MethodsWe retrospectively analyzed data from 129 patients with asthma that were prescribed zileuton at the University of Pittsburgh's Comprehensive Lung Clinic. A total of 75 patients from the above population had requisite lung function data and zileuton usage that would help assess a drug response effect. A zileuton responder was defined as having at least or greater than 5% annualized increase in post-bronchodilator FEV1% from baseline. Using a multivariate logistic regression analysis, we determined the association between responder status and the underlying phenotypic characteristics.ResultsUsing generalized estimating equations (GEE) analysis of 331 individual lung function test data-points as well as logistic regression analysis for predictors of 5% or more annualized increase in FEV1%, 21 of 75 patients (28%) met criteria for having a differential response to zileuton. Severe asthma was associated less often with responder status (OR 0.12; p 0.004). Obesity was less often associated with responder status, however did not reach significance (OR 0.46; p 0.15).ConclusionIn this retrospective study, zileuton response varies across asthmatics, with poorer response rates being associated with those with severe asthma and possibly obesity. Although prescription trends for zileuton may predominate amongst severe asthmatics, this tendency does not seem to mirror the actual likelihood to respond. As against the trivial role for zileuton per current GINA algorithms, our study brings forward a notion that zileuton may well be considered along with LTRAs (like montelukast) for non-severe asthma.
       
  • Treatment response according to small airways disease status: The effects
           of high-strength extrafine pMDI beclomethasone dipropionate/formoterol
           fumarate in fixed dose combination in moderate uncontrolled asthmatic
           patients
    • Abstract: Publication date: February 2020Source: Pulmonary Pharmacology & Therapeutics, Volume 60Author(s): Giovanna E. Carpagnano, Giulia Scioscia, Donato Lacedonia, Silvia Romana Stornelli, Carla Maria Irene Quarato, Piera Soccio, Onofrio Resta, Maria Pia Foschino BarbaroAbstractBackgroundInflammation in small airways is particularly clinically active in severe asthma but they still continue to be ignored as considered silent. Recently, the Atlantis study reports small airways involvement in 91% of the asthma population. Therefore in the era of phenotype driven therapy, the aim of this study was to verify if high-strength extrafine ICS/LABA in fixed dose increases clinical efficacy in moderate asthmatic patients with small airways dysfunction and it could be proposed as phenotype driven therapy.MethodsIn this prospective, non-interventional, real-life pilot study we enrolled 37 consecutive patients with moderate asthma who were uncontrolled despite GINA step 3 treatment. All subjects at enrollment were divided in two groups according to the presence of small airways dysfunction:1) small airways phenotype (SAP) group: smokers (≥10 packs/die), ex-smokers (>20 packs/year) with air trapping (FVC 100% - FEF 25–75%
       
  • Impact of Azathioprine use in chronic hypersensitivity pneumonitis
           patients
    • Abstract: Publication date: February 2020Source: Pulmonary Pharmacology & Therapeutics, Volume 60Author(s): André Terras Alexandre, Natália Martins, Sara Raimundo, Natália Melo, Patrícia Catetano Mota, Hélder Novais e Bastos, José Miguel Pereira, Rui Cunha, Susana Guimarães, Conceição Souto Moura, António MoraisAbstractIntroductionSystemic corticosteroids are widely used in chronic hypersensitivity pneumonitis (CHP); however, there is not much evidence to support their use, besides being associated with significant side effects. Azathioprine (AZA) use is common in CHP, although not prospectively tested in randomized controlled trials. Our objective was to evaluate the lung function trajectory of CHP patients after AZA initiation, as well as to assess the safety profile of this drug.MethodsRetrospective analysis of patients initiated on AZA following a multidisciplinary team diagnosis of CHP. The longitudinal trajectory of lung function in the first 2 years of treatment was assessed.ResultsThirty-five out of 62 patients (56.5%) remained on treatment after 2 years. AZA treatment was associated with a significant improvement in forced vital capacity (FVC) at 12 and 24 months (p = 0.015 and p 
       
  • FEV1 recovery following methacholine challenge in asthma: Variability and
           comparison of methods
    • Abstract: Publication date: February 2020Source: Pulmonary Pharmacology & Therapeutics, Volume 60Author(s): Dave Singh, Naimat Khan, James Dean, Andrew Fowler, Abhya Gupta, Verena Endriss, Philippe Iacono, Bernd DisseAbstractBackgroundMethacholine challenges have been used in clinical trials to assess therapeutic effects and potential adverse reactions of interventions on pulmonary function in a sensitive population, such as in subjects with asthma. Here, we evaluate the variability of the methacholine challenge recovery model, and compare the results obtained for both incremental and bolus challenge methods.MethodsThe extent, time course and variability of change in forced expiratory volume in 1 s (FEV1) following repeated methacholine challenges in subjects with mild asthma were investigated in an open-label, four-period, fixed-sequence, two-method, replicate crossover study. At Visits 1 and 2, subjects underwent an incremental challenge using doubling doses of methacholine until a ≥20% decrease in FEV1 was observed; at Visits 3 and 4, subjects underwent a bolus challenge, inhaling a single dose of methacholine calculated from the cumulative dose established during Visit 1.ResultsA total of 19 subjects were included in the study. Both the mean FEV1 area under the curve (FEV1 AUC0–tz) and mean maximum reductions in FEV1 (absolute and relative) 120 min post-challenge values were higher for the incremental challenges than the bolus challenges, with no reported difference between repetitions of the same methodology. FEV1 AUC0–tz decrease 120 min post challenge demonstrated an intra-subject coefficient of variation (CV) of 47.2% (incremental) and 78.3% (bolus), suggesting considerable between-visit variability. The mean absolute, and similarly relative, maximum reductions in FEV1 compared with post-diluent baseline values demonstrated lower intra-subject variability (incremental 21.16%, bolus 40.67%) than the FEV1 AUC0–tz-based endpoint.There was a trend towards faster recovery following the bolus challenge than with the incremental challenge. The provocative dose of methacholine inducing a ≥20% decrease in FEV1 resulted in a between-group mean difference of 27.20% in the incremental challenge periods, with a high intra-subject CV of 80.64%, demonstrating considerable variability.ConclusionMaximum reduction in FEV1 had the lowest variability. There was little difference between repetitions of the same methodology, as indicated by overlapping confidence intervals. There was a trend towards faster recovery following bolus challenge than with the incremental challenge. The results of this trial could be of value when designing future clinical trials using the methacholine challenge methodology.
       
  • Prospective evAluatIon foR inhalation devices in Greek patients with COPD
           and asthma: The PAIR study
    • Abstract: Publication date: February 2020Source: Pulmonary Pharmacology & Therapeutics, Volume 60Author(s): Theodoros Karampitsakos, Georgios Hillas, Eleftherios Zervas, Petros Bakakos, Grigorios Stratakos, Katerina Dimakou, Efrosyni Manali, Demosthenes Bouros, Spyridon Papiris, Argyrios Tzouvelekis, Vasilios Adamidis, Helen Adamou, Xenophon Agelidis, Konstantinos Albantakis, Aikaterini Anaplioti, Christos Babalis, George Balasoulis, Konstantinos Christou, Christina Filippidou, Emmanuel FothiantakisAbstractIntroductionChronic obstructive pulmonary disease (COPD) and asthma remain a major health burden. Adherence to inhaled therapy is critical in order to optimize treatment effectiveness. Properly designed questionnaires can assess patients’ satisfaction with their inhaler devices.Patients and methodsA total of 766 patients with COPD, asthma or Asthma-COPD Overlap (ACO) were initially enrolled. During their first visit, patients were classified into three groups (Diskus™, Elpenhaler®, Turbuhaler®). Patients completed the FSI-10 questionnaire on Day 0 and Day 60. Test-retest reliability was evaluated.ResultsA total of 705 patients completed the study. FSI-10 questionnaire had good test-retest reliability (Total Intraclass Correlation Coefficient: 0.86). All dry powder inhaler (DPIs) yielded satisfactory results. Median score of FSI-10 questionnaire in first visit (FSI-10-I) was significantly higher for patients receiving Elpenhaler® (45, 95% CI: 44 to 46) than patients receiving Diskus™ (42, 95% CI: 41 to 43) and Turbuhaler® (42, 95% CI: 41 to 43) (p 
       
  • Low penetrance of antibiotics in the epithelial lining fluid. The role of
           inhaled antibiotics in patients with bronchiectasis
    • Abstract: Publication date: February 2020Source: Pulmonary Pharmacology & Therapeutics, Volume 60Author(s): Theodoros Karampitsakos, Ourania Papaioannou, Maria Kaponi, Andreana Kozanidou, Georgios Hillas, Elisavet Stavropoulou, Demosthenes Bouros, Katerina DimakouAbstractPlasma drug concentrations, spectrum of antibacterial activity and minimum inhibitory concentration (MIC) had been widely considered as markers of the efficacy of antibiotics. Nonetheless, in several cases, antibiotics characterized by all these features were ineffective for the treatment of respiratory tract infections. A typical paradigm represented the case of patients with bronchiectasis who do not always benefit from antibiotics and thus experiencing increased sputum production, worse quality of life, more rapid forced expiratory volume in the first second (FEV1) decline, more frequent exacerbations and increased mortality rates, especially those with Pseudomonas aeruginosa (P. aeruginosa) chronic infection. Subsequently, penetrance of antibiotics in the epithelial lining fluid has gradually emerged as another key factor for the outcome of antibiotic treatment. Given that a plethora of antibiotics presented with poor or intermediate penetrance in the epithelial lining fluid, inhaled antibiotics targeting directly the site of infection emerged as a new option for patients with respiratory disorders including patients with bronchiectasis. This review article intends to summarize the current state of knowledge for the penetrance of antibiotics in the epithelial lining fluid and present results from clinical trials of inhaled antibiotics in patients with bronchiectasis of etiology other than cystic fibrosis.
       
  • The leukotriene receptor antagonist Montelukast can induce adverse skin
           reactions in asthmatic patients
    • Abstract: Publication date: February 2020Source: Pulmonary Pharmacology & Therapeutics, Volume 60Author(s): Eleonora Di Salvo, Vincenzo Patella, Marco Casciaro, Sebastiano GangemiAbstractMontelukast the leukotriene receptor antagonist is an anti-inflammatory drug that causes bronchodilation and for this reason it is used to improve inflammatory states in asthma and allergic rhinitis. Montelukast is generally considered a safe drug with the occurrence of a few adverse drug reactions (ADRs) and anti-leucotrienes are usually well-tolerated by adults and young patients. Starting from these premises the purpose of this review is so give un up-to-date scenario about skin adverse reactions due to Montelukast administration. Only few cases were reported during last years, however interestingly some recent reports let us enlarging our ADR data about Montelukast. We decided to divide the paragraph into sections evaluating the following skin lesions: vasculitic lesions, rash, urticaria and angioedema. As described in the results, CSS were the most frequent cases reported, belonging to the Vasculitis category. We speculated several mechanisms leading to the spread of the skin reactions. Montelukast still remains a safe drug used for the treatment of severe and moderate asthma. However, for some reasons still in course of analysis, in rare cases patients could develop ADR. Among these, about half of the patients show skin signs as rash, vescicles, bullous skin, purpura, maculopapular cutis, erythematous exanthema, urticaria and angioedema. Most of these symptoms are a consequence of the onset of a vasculitis as CSS and allergic granulomatous angiitis. In many cases the onset of the reactions happen within the first months of intake. For this reason, the prescribing physicians should be alert for signs, symptoms and genetic predisposition of these skin diseases.
       
  • Asthma phenotypes and T-bet protein expression in cells treated with
           Fluticasone Furoate/Vilanterol
    • Abstract: Publication date: Available online 7 January 2020Source: Pulmonary Pharmacology & TherapeuticsAuthor(s): Zahra Alizadeh, Esmaeil Mortaz, Marzieh Mazinani, Mohammad Reza Fazlollahi, Hassan Heidarnezhad, Ian Adcock, Mostafa MoinAbstractAsthma is a complex disease with diverse clinical manifestations ranging from mild to severe. Despite existing guidelines for asthma recognition and treatment, still a proportion of patients stay uncontrolled. Combinational therapy which comprises inhaled corticosteroids (ICS) and a long acting B2 adrenreceptor agonist (LABA) has been suggested to control asthma. In this study T-bet expression was attested in CD4 T cells treated with Fluticasone Furoate (FF), Vilanterol (V) and FF/V combination in severe asthmatic patients compared to patients with moderate asthma and healthy controls using Immunocytochemistry (ICC). First, CD4 T cells were isolated from PBMCs of 12 patients and controls using CD4 T cell isolation kit. Subsequently, isolated CD4 T cells were cultured with FF, V and FF/V for 1 h. To accomplish ICC, cells were incubated with anti-T-bet antibody, and then stained with HRP-bound secondary antibody. T-bet expression was evaluated using light microscopy. Statistical analyses were performed using R 3.5.2 software and visualized by ggplot2 3.1.0 package. Significant increasing in T-bet expression was seen in CD4 T cells from patients with moderate asthma treated with FF and FF/V. Suggesting conclusion would be distinct mechanisms responsible for severe asthma and moderate asthma in the patients and the needs for novel therapies. Further molecular studies in different asthma phenotypes would be instructive for asthma treatment.
       
  • The small quinolone derived compound HT61 enhances the effect of
           tobramycin against Pseudomonas aeruginosa in vitro and in vivo
    • Abstract: Publication date: Available online 27 December 2019Source: Pulmonary Pharmacology & TherapeuticsAuthor(s): R.T. Amison, M.-E. Faure, B.G. O'Shaughnessy, K.D. Bruce, Y. Hu, A. Coates, C.P. PageAbstractHT61 is a small quinolone-derived compound previously demonstrated to exhibit bactericidal activity against gram-positive bacteria including methicillin-susceptible Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA). When combined with the classical antibiotics and antiseptics neomycin, gentamicin, mupirocin and chlorhexidine, HT61 demonstrated synergistic bactericidal activity against both MSSA and MRSA infections in vitro. In this study, we investigated the individual antimicrobial activity of HT61 alongside its capability to increase the efficacy of tobramycin against both a tobramycin sensitive laboratory reference strain (PAO1) and tobramycin resistant clinical isolates (RP73, NN2) of the gram-negative bacteria Pseudomonas aeruginosa (P. aeruginosa). Using broth microdilution methods, the MICs of HT61 against all strains were assessed, as well as the effect of HT61 in combination with tobramycin using both the chequerboard method and bacterial time-kill assays. A murine model of pulmonary infection was also used to evaluate the combination therapy of tobramycin and HT61 in vivo. In these studies, we demonstrated significant synergism between HT61 and Tobramycin against the tobramycin resistant P. aeruginosa strains RP73 and NN2, whilst an additive/intermediate effect was observed for P. aeruginosa strain PA01 which was further confirmed using bacterial time kill analysis. In addition, the enhancement of tobramycin by HT61 was also evident in in vitro assays of biofilm eradication. Finally, in vivo studies revealed analogous effects to those observed in vitro with HT61 when administered in combination with tobramycin against each of the three P. aeruginosa strains at the highest tested dose (10 mg/kg).
       
  • Pharmacokinetics of budesonide/glycopyrrolate/formoterol fumarate metered
           dose inhaler formulated using co-suspension delivery technology after
           single and chronic dosing in patients with COPD
    • Abstract: Publication date: Available online 10 December 2019Source: Pulmonary Pharmacology & TherapeuticsAuthor(s): Leonard J. Dunn, Edward M. Kerwin, Kiernan DeAngelis, Patrick Darken, Michael Gillen, Paul DorinskyAbstractBackgroundBudesonide/glycopyrrolate/formoterol fumarate metered dose inhaler (BGF MDI), formulated using co-suspension delivery technology, is a triple fixed-dose combination in late-stage clinical development for chronic obstructive pulmonary disease (COPD).MethodsWe conducted two studies to characterize the pharmacokinetic (PK) profile of BGF MDI in patients with COPD: (i) a phase I, open-label, single and chronic (7-day) dosing study (NCT03250182) with one treatment arm (BGF MDI 320/18/9.6 μg); and (ii) a PK sub-study of KRONOS (NCT02497001), a phase III, randomized, double-blind study in which patients received 24 weeks’ treatment with BGF MDI 320/18/9.6 μg, glycopyrrolate/formoterol fumarate (GFF) MDI 18/9.6 μg, budesonide/formoterol fumarate (BFF) MDI 320/9.6 μg, or budesonide/formoterol fumarate dry powder inhaler (BUD/FORM DPI) 320/9 μg. PK parameters in both studies included maximum observed plasma concentration (Cmax) and area under the plasma concentration–time curve from 0 to 12h (AUC0–12).ResultsIn the phase I PK study (30 patients), budesonide and glycopyrronium Cmax were comparable after single and chronic dosing of BGF MDI (accumulation ratio [RAC] 95% and 107%, respectively) whereas Cmax for formoterol was slightly higher after chronic dosing (RAC 116%). AUC0–12 for budesonide, glycopyrronium, and formoterol were higher following chronic versus single dosing, with an RAC of 126%, 179%, and 143%, respectively. After 7 days’ dosing, AUC0–12 and Cmax for all three components of BGF MDI were similar to those in the KRONOS PK sub-study (202 patients) at Week 24.In the latter sub-study, Cmax and AUC0–12 at Week 24 were generally comparable across treatments for budesonide (geometric mean ratios [GMR] of 96%–109% for BGF MDI vs BFF MDI or BUD/FORM DPI), glycopyrronium (GMR of 88%–100% for BGF MDI vs GFF MDI), and formoterol (GMR of 80%–113% for BGF MDI vs GFF MDI or BFF MDI).ConclusionsSteady-state PK parameters of budesonide, glycopyrronium, and formoterol were similar after 7 days’ dosing in the phase I PK study and after 24 weeks in the KRONOS PK sub-study. Systemic exposure to budesonide, glycopyrronium, and formoterol was generally comparable across treatments in the KRONOS PK sub-study, suggesting no meaningful drug–drug or within-formulation PK interactions.
       
  • Real-world evaluation of the clinical safety and efficacy of
           fluticasone/formoterol FDC via the Revolizer® in patients with persistent
           asthma in India
    • Abstract: Publication date: Available online 30 November 2019Source: Pulmonary Pharmacology & TherapeuticsAuthor(s): Aloke Ghoshal, Pradyut Waghray, George Dsouza, Mahip Saluja, Mayank Agarwal, Ashish Goyal, Sneha Limaye, Akash Balki, Sudhir Bhatnagar, Manish Jain, Sharad Tikkiwal, Abhijit Vaidya, Meena Lopez, Rashmi Hegde, Jaideep GogtayAbstractThe combination of inhaled corticosteroids (ICS) and long-acting beta2-agonists (LABAs) is widely used for the management of asthma. This prospective, open-label, non-comparative, observational, 24-week multicentre study is the first real-world study from India to compare the efficacy and safety of fixed-dose combination of fluticasone/formoterol (Maxiflo® 100/6 mcg or 250/6 mcg) capsules via the Revolizer® device in patients with persistent asthma. The primary efficacy analyses included mean change in Asthma Control Test (ACT™) at 4, 8, 16 and 24 weeks. Secondary efficacy analyses included mean change in morning and evening peak expiratory flow rate (PEFR) at the end of 4, 8, 16 and 24 weeks, number of patients having symptom-free days and nights at the end of 4, 8, 16 and 24 weeks, the number and severity of exacerbations over 24 weeks and response to the Usability Preference Satisfaction Confidence questionnaire after 1 week. Overall, 385 (of 401; 96.01%) enrolled patients completed the study. The mean change in ACT™ score was 6.7 ± 3.71 (95% CI: 6.32, 7.06; p 
       
  • Bronchoscopic delivery of aminocaproic acid as a treatment for pulmonary
           bleeding: A case series
    • Abstract: Publication date: February 2020Source: Pulmonary Pharmacology & Therapeutics, Volume 60Author(s): Russell P. Simon, Clara Oromendia, Lourdes M. Sanso, Liz G. Ramos, Kapil RajwaniAbstractObjectiveBronchoscopy is an essential therapeutic modality in the treatment of pulmonary bleeding. Although numerous endoscopic treatments exist, topical ε-aminocaproic acid has not been described in the literature. This study documents the use of this novel treatment for pulmonary bleeding and compares it to available evidence for tranexamic acid, a similar anti-fibrinolytic agent.DesignCase-series study.SettingICU and general inpatient floors of a tertiary medical center.PatientsForty-six patients receiving endobronchial ε-aminocaproic acid for the treatment or prevention of pulmonary bleeding.Measurements and main resultsOf the 46 patients included in the study, 41.6% and 13% presented with non-massive and massive hemoptysis, respectively. In patients with active pulmonary bleeding, endobronchial application of ε-aminocaproic acid and accompanying therapies resulted in cessation of bleeding in 94.7% of cases. A total of six patients received ε-aminocaproic acid monotherapy; in three patients with active bleeding, 100% achieved hemostasis after treatment. Of the 36 patients successfully treated for active pulmonary bleeding, 27.8% had recurrent bleeding within 30 days. Thirty-day adverse events were as follows: death (10 patients), deep vein thrombosis (2 patients), renal failure (2 patients), and stroke (2 patients).ConclusionsEndobronchial administration of ε-aminocaproic acid during bronchoscopy may be a safe and efficacious option in the treatment and prevention of pulmonary bleeding. Further studies are necessary to better define ε-aminocaproic acid's safety profile, optimal routes of administration, and comparative effectiveness to tranexamic acid.
       
  • C-reactive protein as a biomarker of response to inhaled corticosteroids
           among patients with COPD
    • Abstract: Publication date: Available online 27 November 2019Source: Pulmonary Pharmacology & TherapeuticsAuthor(s): Olorunfemi A. Oshagbemi, Frits M.E. Franssen, Emiel F.M. Wouters, Anke H. Maitland-van der Zee, Johanna H.M. Driessen, Anthonius de Boer, Frank de VriesAbstractAimsC-reactive protein (CRP) is an important biomarker in systemic inflammation in COPD; reports have suggested inhaled corticosteroids (ICS) attenuate CRP levels. We evaluated the risk of moderate-to-severe exacerbations, severe exacerbations and all-cause mortality among patients with COPD currently exposed to Inhaled corticosteroids (ICS) stratified by CRP levels compared to never ICS users with low CRP levels.MethodsWe included subjects age 40 or more who had a diagnosis of COPD from January 1, 2005 to January 31, 2014 from the UK Clinical Practice Research Datalink (CPRD). ICS exposure was determined time-dependently, as current, recent, past or never users. We evaluated the risk of moderate-to-severe exacerbations, severe exacerbations and all-cause mortality among ICS users stratified by CRP levels.Results17,722 subjects diagnosed with COPD met the inclusion criteria. Among current or never ICS with elevated CRP levels we found, no significantly reduced risk of moderate-to-severe or severe exacerbations. For patients currently exposed ICS with CRP levels ≥8 mg/L there was no reduced risk of moderate-to-severe exacerbations (adjusted hazard ratio [adj. HR] 0.99; 95% confidence interval [CI] 0.76–1.31) or severe exacerbations (adj.HR 1.52; 95% CI 0.71–3.27). However, we found an increased risk of all-cause mortality among COPD patients with CRP levels ≥8 mg/L irrespective of ICS exposure.ConclusionWe did not find a reduced risk of moderate and/or severe COPD exacerbations among COPD patients with varying CRP levels currently exposed to ICS. However, low-grade systemic inflammation was associated with all-cause mortality among COPD patients.
       
  • Inhibition of the PD-1/PD-L1 signaling pathway enhances innate immune
           response of alveolar macrophages to mycobacterium tuberculosis in mice
    • Abstract: Publication date: Available online 18 September 2019Source: Pulmonary Pharmacology & TherapeuticsAuthor(s): Jin-Fang Hu, Wei Zhang, Wei Zuo, Hao-Qu Tan, Wei BaiAbstractBackgroundMycobacterium tuberculosis (TB) is a pathogen that consequently leads to TB infection, which remains a significant global health concern. Programmed death 1 (PD-1)/programmed death-ligand 1 (PD-L1) signaling pathway is critical for terminating immune responses. The present study aimed to elucidate the regulatory role of the PD-1/PD-L1 signaling pathway in alveolar macrophages against Mycobacterium TB in mice.MethodsSpecific pathogen free mice were initially prepared for Mycobacterium TB model establishment. The alveolar macrophages of the successfully modeled rats were evaluated to determine the levels of PD-1, PD-L1, AKT, mTOR, TNF-α, NF-κB, IL-2, IL-4, IL-6, IL-10, IL-17, IL-17A, and IFN-γ. The surface makers of macrophages (CD11c, CD16, CD86, CD163, CD206, CX3CR-1 and CSF-1R), level of ROS, apoptosis and cell cycle, were all assessed.ResultsElevated levels of PD-1 and PD-L1, decreased levels of AKT and mTOR, along with elevated levels of TNF-α, NF-κB, IL-17, IL-2, IL-6, IL-17A and IFN-γ were identified in the alveolar macrophages infected with Mycobacterium TB, while an opposite trend was observed when PD-1/PD-L1 signaling pathway was inhibited. Additionally, elevated protein levels of CD11c, CD16 and CD86, as well as an increased rate of positive ROS and cell apoptosis, levels of Bax, and a diminished percentage of alveolar macrophages at the S and G2/M stages were detected in the event of Mycobacterium TB infection. A contrasting trend to the aforementioned findings was detected when the PD-1/PD-L1 signaling pathway was inhibited.ConclusionTaken together, these results suggested that inhibition of the PD-1/PD-L1 signaling pathway enhanced the innate immune response of alveolar macrophages to Mycobacterium TB in mice.
       
 
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