scholarly journals Adult cystic fibrosis: association of acute pulmonary exacerbations and increasing severity of lung disease with auxotrophic mutants of Pseudomonas aeruginosa.

Thorax ◽  
1993 ◽  
Vol 48 (10) ◽  
pp. 1002-1005 ◽  
Author(s):  
R F Taylor ◽  
M E Hodson ◽  
T L Pitt
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Lung Disease ◽  
Auxotrophic Mutants ◽  
Pulmonary Exacerbations

scholarly journals Type-4 Phosphodiesterase (PDE4) Blockade Reduces NETosis in Cystic Fibrosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Licia Totani ◽  
Concetta Amore ◽  
Antonio Piccoli ◽  
Giuseppe Dell’Elba ◽  
Angelo Di Santo ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Lung Disease ◽  
Pde4 Inhibitor ◽  
Free Dna ◽  
Impaired Lung Function ◽  
Cellular Integrity ◽  
Net Release

Neutrophilic inflammation is a key determinant of cystic fibrosis (CF) lung disease. Neutrophil-derived free DNA, released in the form of extracellular traps (NETs), significantly correlates with impaired lung function in patients with CF, underlying their pathogenetic role in CF lung disease. Thus, specific approaches to control NETosis of neutrophils migrated into the lungs may be clinically relevant in CF. We investigated the efficacy of phosphodiesterase (PDE) type-4 inhibitors, in vitro, on NET release by neutrophils from healthy volunteers and individuals with CF, and in vivo, on NET accumulation and lung inflammation in mice infected with Pseudomonas aeruginosa. PDE4 blockade curbed endotoxin-induced NET production and preserved cellular integrity and apoptosis in neutrophils, from healthy subjects and patients with CF, challenged with endotoxin, in vitro. The pharmacological effects of PDE4 inhibitors were significantly more evident on CF neutrophils. In a mouse model of Pseudomonas aeruginosa chronic infection, aerosol treatment with roflumilast, a selective PDE4 inhibitor, gave a significant reduction in free DNA in the BALF. This was accompanied by reduced citrullination of histone H3 in neutrophils migrated into the airways. Roflumilast-treated mice showed a significant improvement in weight recovery. Our study provides the first evidence that PDE4 blockade controls NETosis in vitro and in vivo, in CF-relevant models. Since selective PDE4 inhibitors have been recently approved for the treatment of COPD and psoriasis, our present results encourage clinical trials to test the efficacy of this class of drugs in CF.

scholarly journals Telephone surveillance during 2019 novel coronavirus disease: Is it a helpful diagnostic tool for detecting acute pulmonary exacerbations in children with chronic lung disease?

2020 ◽  
pp. 1357633X2097200
Author(s):  
Beste Ozsezen ◽  
Nagehan Emiralioglu ◽  
Dilber A Tural ◽  
Birce Sunman ◽  
Halime N Buyuksahin ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Transmission Risk ◽  
Nutrition Status ◽  
Peak Time ◽  
Pulmonary Exacerbation ◽  
Pulmonary Exacerbations ◽  
The Times ◽  
Novel Coronavirus

Introduction The global burden of the 2019 novel coronavirus disease pandemic on the healthcare system, as well as the high transmission risk of coronavirus disease has led to the use of alternative strategies for evaluation of children with chronic conditions. In this context, telemedicine has become the effective and affordable choice. In this study we aimed to evaluate the efficiency of telephone visits to determine pulmonary exacerbations and hospitalization rates of children with cystic fibrosis and interstitial lung disease. Methods A total of 119 children with cystic fibrosis or interstitial lung disease were enrolled and provided cases in which telephone visits were applied during the peak time of the coronavirus disease pandemic in our country. The recordings of respiratory, gastrointestinal and other symptoms, nutrition status, rate of acute pulmonary exacerbation, treatments initiated by telephone visits, referral to hospital and hospitalization were established from the electronic health reports of the patients. Results Thirteen patients (10.9%) were symptomatic, 12 of them (10%) were diagnosed with acute pulmonary exacerbation. One patient was diagnosed with peripheral facial paralysis. Nine patients were recalled to the hospital and seven patients (5.8%) were hospitalised. Discussion Using telemedicine the health status of patients can be defined, and patients can be guided on proper healthcare that they need, especially during the times of pandemics which we are facing. Communication with patients while minimising the risk of exposure to coronavirus disease is an important advantage of telemedicine. Telemedicine will have to be implemented on our daily medical practice in the near future.

scholarly journals Pseudomonas aeruginosa Susceptibility Patterns and Associated Clinical Outcomes in People with Cystic Fibrosis following Approval of Aztreonam Lysine for Inhalation

2020 ◽  
pp. AAC.02327-20 ◽  
Author(s):  
Claire L Keating ◽  
Jonathan B Zuckerman ◽  
Pradeep K Singh ◽  
Matthew McKevitt ◽  
Oksana Gurtovaya ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Lung Function ◽  
Clinical Outcomes ◽  
Primary Endpoint ◽  
The United States ◽  
Study Endpoint ◽  
Primary Study ◽  
Antibiotic Exposure ◽  
Pulmonary Exacerbations

Rationale: Approval of aztreonam lysine for inhalation solution (AZLI) raised concerns that additional antibiotic exposure would potentially affect susceptibility profiles of Pseudomonas aeruginosa (PA) isolates from cystic fibrosis (CF) patients.Objective: This 5-year, prospective, observational study tracked susceptibility changes and clinical outcomes in CF patients in the United States with chronic PA infection.Methods: Sputum cultures were collected annually (2011-2016). The primary study endpoint was the proportion of subjects whose least susceptible PA isolate had an aztreonam minimum inhibitory concentration (MIC) that was >8 μg/mL (parenteral breakpoint) and increased ≥4-fold compared with the least susceptible isolate from the previous year. Annualized data for pulmonary exacerbations, hospitalizations, and FEV1% predicted were obtained from the CF Foundation Patient Registry and compared between subjects meeting/not meeting the primary endpoint.Results: 510 subjects were enrolled; 334 (65%) completed the study. A consistent proportion of evaluable subjects (13-22%) met the primary endpoint each year; and AZLI use during the previous 12 months was not associated with meeting the primary endpoint. While the annual decline in lung function was comparable for subjects meeting/not meeting the primary endpoint, more pulmonary exacerbations and hospitalizations were experienced by those who met it.Conclusions: Aztreonam susceptibility of PA remained consistent during the 5-year study. The relationship between PA isolate susceptibilities and clinical outcomes is complex; reduced susceptibility was not associated with accelerated decline in lung function, but was associated with more exacerbations and hospitalizations, likely reflecting increased overall antibiotic exposure.

scholarly journals Early-Life Pseudomonas aeruginosa Infection in Cystic Fibrosis and Lung Disease Progression

2017 ◽  
Vol 4 ◽  
pp. 2333794X1773846
Author(s):  
Argyri Petrocheilou ◽  
Maria Papagrigoriou-Theodoridou ◽  
Athanasios Michos ◽  
Stavros-Eleftherios Doudounakis ◽  
Ioanna Loukou ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Lung Disease ◽  
Disease Progression ◽  
Early Life ◽  
Pseudomonas Aeruginosa Infection

scholarly journals Pseudomonas aeruginosa in cystic fibrosis: Pyocyanin negative strains are associated with BPI-ANCA and progressive lung disease

2011 ◽  
Vol 10 (4) ◽  
pp. 265-271 ◽  
Author(s):  
Malin Carlsson ◽  
Swati Shukla ◽  
Ann Cathrine Petersson ◽  
Mårten Segelmark ◽  
Thomas Hellmark
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Lung Disease

scholarly journals An 8 week open-label interventional multicenter study to evaluate the lung clearance index as endpoint for clinical trials in cystic fibrosis patients ≥8 years of age, chronically infected with Pseudomonas aeruginosa

2020 ◽  
Author(s):  
Sivagurunathan Sutharsan ◽  
Susanne Naehrig ◽  
Uwe Mellies ◽  
Christian Sieder ◽  
joerg Zeigler
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Lung Function ◽  
Lung Disease ◽  
Small Airways ◽  
Open Label ◽  
Lung Clearance ◽  
Efficacy Trials ◽  
Inhaled Antibiotics ◽  
Lung Clearance Index

Abstract Background Forced expiratory volume in 1 second (FEV 1 ) is the only parameter currently recognized as a surrogate endpoint in cystic fibrosis (CF) trials. However, FEV 1 is relatively insensitive to changes in the small airways of patients with milder lung disease. This pilot study aimed to evaluate the lung clearance index (LCI) as a marker for use in efficacy trials with inhaled antibiotics in CF. Methods This open-label, single-arm study enrolled CF patients with Pseudomonas aeruginosa infection, who were treated with tobramycin (28-day on/off regime). FEV 1 , LCI and bacterial load in sputum (CFU) were assessed at baseline, after 1, 4 and 8 weeks of treatment. Results All patients (n=17) showed elevated LCI of >11 despite 3 patients having normal FEV 1 (>90% predicted) at baseline. Overall, LCI improved in 8 (47%) patients and FEV 1 in 9 (53%) patients. At week 4, LCI improved by 0.88, FEV 1 increased by 0.52%, and P. aeruginosa reduced by 30481.3 CFU/mL. These changes were however statistically non-significant. Six adverse events occurred in 5/17 (29.4%) patients, most of which were mild-to-moderate in severity. Conclusions Due to the low evaluable sample size, no specific trend was observed related to the changes between LCI, FEV1 and CFU. Based on the individual data from this study and from recently published literature, LCI has been shown to be a more sensitive parameter than FEV1 for lung function. LCI can hypothesized to be an appropriate endpoint for efficacy trials in CF patients if the heterogeneity in lung function is limited by enrolling younger patients or patients with more milder lung disease and thus, limiting the ventilation inhomogeneities. Trial registration : The study is registered with ClinicalTrials.gov, identifier: NCT02248922

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