Azithromycin inhibits constitutive airway epithelial sodium channel activation in vitro and modulates downstream pathogenesis in vivo.

We examined whether macrolides could modulate constitutive ENaC activity and downstream events that typify cystic fibrosis (CF) and chronic obstructive pulmonary diseases (COPD) in in vitro and in vivo models of ENaC overexpression. Treatment of ENaC-overexpressing human bronchial epithelial cells (β/γENaC-16HBE14o- cells) with three macrolides (erythromycin, clarithromycin, azithromycin) confirmed dose-dependent suppression of ENaC function. For in vivo studies, mice harboring airway specific βENaC overexpression (C57BL/6J-βENaC-Tg mice) were treated orally with azithromycin, a well-established antimicrobial agent that has been widely prescribed. Azithromycin treatment modulated pulmonary mechanics, emphysematous phenotype and pulmonary dysfunction. Notably, a lower dose (3 mg kg-1) of azithromycin significantly increased forced expiratory volume in 0.1 second (FEV0.1), an inverse indicator of bronchoconstriction. Although not statistically significant, improvement of pulmonary obstructive parameters such as emphysema and lung dysfunction (FEV0.1%) was observed. Our results demonstrate that macrolides directly attenuate constitutive ENaC function in vitro and may be promising for the treatment of obstructive lung diseases with defective mucociliary clearance, possibly by targeting ENaC hyperactivation. PMID: 32009028 [PubMed - as supplied by publisher]
Source: Biological and Pharmaceutical Bulletin - Category: Drugs & Pharmacology Authors: Tags: Biol Pharm Bull Source Type: research

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Publication date: Available online 13 February 2020Source: Pharmacology &TherapeuticsAuthor(s): Kylie B.R. Belchamber, Louise E. DonnellyAbstractChronic pulmonary conditions now account for 1 in 15 deaths in the US and mortality is increasing. Chronic obstructive pulmonary disease (COPD) is due to become the 3rd largest cause of mortality by 2030 and mortality from other respiratory conditions such as asthma, idiopathic pulmonary fibrosis and cystic fibrosis are not reducing. There is an urgent need for novel therapies to address this problem as many of the current strategies targeting inflammation are not sufficient. ...
Source: Pharmacology and Therapeutics - Category: Drugs & Pharmacology Source Type: research
Smoke-measuring smart shirts, breath sound analyzing algorithms, and smart inhalers pave the way of pulmonology and respiratory care into the future. As the number of patients suffering from asthma, COPD, or lung cancer due to rising air pollution and steady smoker-levels will unfortunately not decrease any time soon, we looked around what technology can do to help both patients and caregivers. The results are breathtaking. Attacks of breathlessness are too common The diseases which pulmonologists and respiratory care specialists attempt to fight are among the most common conditions in the modern world – and t...
Source: The Medical Futurist - Category: Information Technology Authors: Tags: Artificial Intelligence Future of Medicine Health Sensors & Trackers AI asthma cancer cancer treatment care COPD diagnostics inhaler lung lung cancer management medical specialty pulmonology respiratory respiratory care Source Type: blogs
ConclusionsTen ‐year survivors were significantly younger, weighed less, and had significantly shorter lengths of hospitalization after transplantation. Bilateral lung transplantation was a significant factor in prolonged survival. Survival also improved with institutional experience
Source: Journal of Cardiac Surgery - Category: Cardiovascular & Thoracic Surgery Authors: Tags: ORIGINAL ARTICLE Source Type: research
A 41-year-old woman with an 8 –pack-year history of tobacco use had 4 years of progressive cough and dyspnea. She had no history of neonatal respiratory distress or nasal congestion and no family history of COPD or cystic fibrosis; pulmonary function testing showed a severe obstruction and chest CT showed lower lobe predominan t emphysema and bronchiectasis. What is the diagnosis and what would you do next?
Source: JAMA - Journal of the American Medical Association - Category: General Medicine Source Type: research
CONCLUSION: These new recommendations, close to French practices, help clinicians to find the right time for referral of patients to transplantation centers. This is crucial for the prognosis of lung transplantation. PMID: 31006579 [PubMed - as supplied by publisher]
Source: Revue des Maladies Respiratoires - Category: Respiratory Medicine Tags: Rev Mal Respir Source Type: research
Abstract Proteases and reactive oxygen species (ROS) have long been implicated in playing key roles in host tissue injury at sites of inflammatory processes dominated by macrophage activations and/or neutrophil infiltrations. Imbalances between proteases/antiproteases and ROS/antioxidants are recognized to contribute to amplification of inflammatory-based host tissue injury. This has been especially well-documented in such respiratory tract diseases as chronic obstructive pulmonary disease, cystic fibrosis, and acute respiratory distress syndrome. Inflammation-related protease/ROS disequilibria are further confoun...
Source: Free Radical Biology and Medicine - Category: Biology Authors: Tags: Free Radic Biol Med Source Type: research
CONCLUSIONS: This study shows the feasibility of phase-resolved functional lung imaging to gain quantitative information regarding regional lung perfusion and ventilation without the need for ultrafast imaging, which will be advantageous for future clinical translation. Magn Reson Med, 2017. © 2017 International Society for Magnetic Resonance in Medicine. PMID: 28856715 [PubMed - as supplied by publisher]
Source: Magnetic Resonance in Medicine - Category: Radiology Authors: Tags: Magn Reson Med Source Type: research
ConclusionsThis study shows the feasibility of phase‐resolved functional lung imaging to gain quantitative information regarding regional lung perfusion and ventilation without the need for ultrafast imaging, which will be advantageous for future clinical translation. Magn Reson Med, 2017. © 2017 International Society for Magnetic Resonance in Medicine.
Source: Magnetic Resonance in Medicine - Category: Radiology Authors: Tags: Note Source Type: research
Antioxidants&Redox Signaling , Vol. 0, No. 0.
Source: Antioxidants and Redox Signaling - Category: Research Authors: Source Type: research
We studied the role of chronic exposure to ambiant air pollution on lung function level and evolution in lung transplant patients.The lung function of 525 lung transplant (LT) patients from the COLT cohort was followed-up. The 12-month average levels of air pollutants (Nitrogen dioxide (NO2), fine particulate matters (PM2.5, PM10) and ozone (O3)) were estimated at the home addresses of each patient. The effect of air pollutant exposure on FEV1 level and change in FEV1 both during the recovery and decline periodes were estimated using mixed linear regression models adjusted on recipient age, sex, smoking (donor and patient)...
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: 6.2 Occupational and Environmental Health Source Type: research
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