Pulmonary Pharmacology & Therapeutics

BACKGROUND: A suboptimal peak inspiratory flow rate (PIFR) in dry-powder inhaler (DPI) users can lead to insufficient therapeutic effects in the treatment of chronic obstructive pulmonary disease (COPD). However, few data on the prevalence of and factors associated with suboptimal PIFR in Korean patients with COPD are available. METHODS: We conducted a cross-sectional study of patients with COPD who had been using DPIs for more than three months. PIFR was measured using an In-Check DIAL G16 device...

BACKGROUND AND OBJECTIVE: Other iatrogenic immunodeficiency-associated lymphoproliferative disorders (OIIA-LPD) are rare but well-known diseases that manifest during or after methotrexate (MTX) administration. Limited information is available on the clinical characteristics of OIIA-LPD of the lung because only a few cases have been reported. Thus, we aimed to assess the incidence and prognosis of patients with OIIA-LPD of the lung. METHODS: Patients with OIIA-LPD of the lung treated at our institution between January 2008 and July 2020 were retrospectively analysed...

BACKGROUND: Acute Respiratory Distress Syndrome (ARDS) is a severe condition with high mortality and morbidity rates. Evidence on the effectiveness of pharmacological interventions for ARDS treatment is limited. Recent studies suggest that aspirin may prevent ARDS development, but its efficacy in established ARDS is uncertain. METHODS: We enrolled patients with ARDS using data from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database. Primary outcomes were 30- and 90-day mortality rates and length of ICU stay...

BACKGROUND: Idiopathic pulmonary fibrosis is a progressive and fatal lung disease lacking effective therapeutics. Treatment with pirfenidone or nintedanib is recommended for patients to delay the progression of their disease. Adverse reactions caused by anti-fibrosis drugs can sometimes interrupt treatment and even change the progression of the disease. OBJECTIVE: This study aimed to investigate the clinical use, adverse reactions, tolerability of pirfenidone and nintedanib in patients with idiopathic pulmonary fibrosis and the efficacy of antifibrotic therapy in a real world...

Pulmonary fibrosis is a complex disease that can occur in a variety of clinical settings. The Zinc Finger and BTB Domain Containing 16 (Zbtb16) is a transcription factor and has not been studied in pulmonary fibrosis. Lung tissues from rats which were treated with bleomycin and Tanshinone IIA (Tan IIA) were collected for mRNA sequencing. Zbtb16, a differentially expressed gene, was screened. Using adeno-associated virus to knock down Zbtb16 in rats, it was found that the lung index and the content of hydroxyproline in lung tissue were decreased...

BACKGROUND: High dose N acetylcysteine (NAC), a mucolytic, anti-inflammatory and antioxidant agent has been shown to significantly reduce exacerbations, and improve quality of life in placebo controlled, double blind randomised (RCT) studies in patients with COPD, and in an open, randomised study in bronchiectasis. In this pilot, randomised, double-blind, placebo-controlled study, we wished to investigate the feasibility of a larger clinical trial, and the anti-inflammatory and clinical benefits of high dose NAC in bronchiectasis...

Pulmonary fibrosis is a progressive and debilitating lung disease characterized by the excessive accumulation of extracellular matrix (ECM) components within the lung parenchyma. However, the underlying mechanism remains largely elusive, and the treatment options available for pulmonary fibrosis are limited. Interleukin 5 receptor, alpha (IL5RA) is a well-established regulator of eosinophil activation, involved in eosinophil-mediated anti-parasitic activities and allergic reactions. Recent studies have indicated additional roles of IL5RA in lung epithelium and fibroblasts...

BACKGROUND: Loss of E-cadherin in the airway epithelial cells is a critical contributor to the development of ALI/ARDS. Yet the underlying mechanisms are largely unknown. Increasing evidences have revealed the significance of ferroptosis in the pathophysiological process of ALI/ARDS. The aim of this study was to investigate the role of ferroptosis in dysregulation of airway epithelial E-cadherin in ALI/ARDS. METHODS: BALB/c mice were subjected to intratracheal instillation of lipopolysaccharide (LPS) to establish an ALI model...

BACKGROUND: Lung transplant recipients (LTRs) have a higher risk of hospitalization and mortality due to COVID-19 compared with the immunocompetent population. The use of nirmatrelvir/ritonavir (NR), an effective oral treatment for COVID-19, is quite challenging due to its potent drug-drug interactions with immunosuppressants and azole antifungals. As there are few clinical reports of the use of NR in LTRs, we measured tacrolimus levels in patients receiving NR in our hospital to improve safety when prescribing NR...

Tyvaso DPI is a drug-device combination therapy comprised of a small, portable, reusable, breath-powered, dry powder inhaler (DPI) for the delivery of treprostinil. It is approved for the treatment of pulmonary arterial hypertension and pulmonary hypertension associated with interstitial lung disease. Tyvaso DPI utilizes single-use prefilled cartridges to ensure proper dosing. Unlike nebulizer devices, administration of Tyvaso DPI is passive and does not require coordination with the device. The low-flow rate design results in targeted delivery to the peripheral lungs due to minimal drug loss from impaction in the oropharynx...

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic, fibrosing interstitial pneumonia of unknown cause that is associated with radiological and/or histological features of usual interstitial pneumonia (UIP). A mean survival of 2-5 years was reported previously to the advent of antifibrotics. According to clinical trials, nintedanib and pirfenidone induce a significant delay in functional decline, with a favorable impact on survival. METHODS: A real-life retrospective and longitudinal study was conducted to assess the efficacy and tolerability of antifibrotics in IPF patients, between January 2014 and December 2020...

INTRODUCTION: The climate crisis poses an immediate threat to human health and well-being, demanding urgent adaptions across sectors, including healthcare. The development of pressurized metered dose inhalers (MDIs) with greater sensitivity to the climate emergency using novel propellants with lower global warming potentials (GWPs), but comparable pharmacokinetic (PK) parameters to currently marketed MDIs, is a vital step toward reducing the impact of healthcare for respiratory disorders on climate change...

INTRODUCTION: Extrafine formulation of beclomethasone/formoterol fixed combination (BDP/F pMDI HFA) is approved for both fixed maintenance and maintenance and reliever therapy (MART) of asthma, and recent data has proven that BDP/F pMDI HFA maintenance and reliever therapy is an effective alternative to other regimens. OBJECTIVE: This study aimed to assess the level of asthma control in a real-life setting in adult patients using extrafine BDP/F pMDI HFA fixed combination in a pressurized metered-dose inhaler (pMDI) as fixed maintenance dosing as well as maintenance and maintenance and reliever therapy...

BACKGROUND: The impact of extracorporeal membrane oxygenation (ECMO) on the pharmacokinetics/dynamics (PK/PD) of beta-lactam antibiotics have not been well studied in general, but cefepime specifically has the least amount of data. We aimed to investigate whether ECMO alters the PK of cefepime in adult intensive care unit (ICU) patients. METHODS: This single-center, retrospective case-control study evaluated cefepime therapeutic drug monitoring (TDM) results from ECMO patients that were matched 1:1 with TDM results in non-ECMO patients for drug regimen and renal function...

Inhaled corticosteroids, along with beta2-agonists and anti-muscarinics, represent the cornerstone of asthma treatment. Although the advent of monoclonal antibodies has dramatically changed severe asthma management, there are still patients ineligible or with poor response to biologics. Moreover, high costs associated with monoclonal antibodies prescription are still an open issue, leading clinicians to carefully assess cost-benefit ratio before their administration. From this perspective, the use of single-inhaler Beclometasone Dipropionate/Formoterol Fumarate/Glycopyrronium in patients with severe asthma could not only improve their clinical and functional performance, but also postpone biologic prescription, with positive repercussions on healthcare costs...

The tyrosine kinase inhibitor nintedanib has been recently approved for the treatment of Interstitial Lung Diseases (ILDs) that manifest a progressive fibrosis phenotype other than Idiopathic pulmonary Fibrosis (IPF). Nintedanib reduces the development of lung fibrosis in various animal models resembling features of PF-ILD and in vitro, it inhibits the fibrosing phenotype of human lung fibroblasts (HLFs) isolated from patients with IPF. To get insight on the cellular and molecular mechanisms that drive the clinical efficiency of nintedanib in patients with non-IPF PF-ILD, we investigated its effects on the fibrosing functions of HLFs derived from patients with PF-hypersensitivity pneumonitis (PF-HP, n = 7), PF-sarcoidosis (n = 5) and pleuroparenchymal fibroelastosis (PPFE, n = 4)...

Pulmonary fibrosis (PF) is a lethal disease characterized by a progressive decline in lung function. Currently, lung transplantation remains the only available treatment for PF. However, both artemisinin (ART) and hydroxychloroquine (HCQ) possess potential antifibrotic properties. This study aimed to investigate the effects and mechanisms of a compound known as Artemisinin-Hydroxychloroquine (AH) in treating PF, specifically by targeting the TGF-β1/Smad2/3 pathway. To do this, we utilized an animal model of PF induced by a single tracheal drip of bleomycin (BLM) in Sprague-Dawley (SD) rats...

Chronic obstructive pulmonary disease (COPD) is a respiratory condition characterized by its heterogeneous nature, progressive course, and significant impact on individuals' quality of life. It is a prevalent global health issue affecting a substantial number of individuals and can pose life-threatening complications if left unmanaged. The development and course of COPD can be influenced by a range of risk factors, including genetic predisposition and environmental exposures. Nevertheless, as researchers adopt a more comprehensive and expansive viewpoint of therapeutic techniques, the associated obstacles become more apparent...

BACKGROUND: Acute lung injury (ALI), along with the more severe condition--acute respiratory distress syndrome (ARDS), is a major cause of respiratory failure in critically ill patients with high morbidity and mortality. Inositol-requiring protein 1α (IRE1α)/X box protein-1 (XBP1) pathway was proved to regulate lipopolysaccharide (LPS)-induced lung injury and inflammation. Yet, its role on epithelial β-catenin in LPS-induced ALI remains to be elucidated. METHODS: LPS-induced models were generated in mice (5 mg/kg) and Beas-2B cells (200 μg/mL)...

INTRODUCTION: The recommended standard dose for α1 -proteinase inhibitor (A1PI) augmentation therapy is 60mg/kg once-weekly (QW) intravenous (IV) infusions that aim to maintain systemic A1PI levels >11μM, the biochemical efficacy threshold, in patients with α1 -antitrypsin deficiency (AATD). However, this standard dose may not be optimal for all patients. Body weight-based dosing, alternative dosing regimens, and treatment interruption periods were evaluated using population pharmacokinetic (PopPK) modeling and simulations...