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Scientific Reports May 2023The rheology of sputum is viewed as a powerful emerging biophysical marker for monitoring muco-obstructive pulmonary diseases such as cystic fibrosis (CF) and non-CF...
The rheology of sputum is viewed as a powerful emerging biophysical marker for monitoring muco-obstructive pulmonary diseases such as cystic fibrosis (CF) and non-CF bronchiectasis (NCFB). However, there is no unified practice to process sputa from collection to analysis, which can lead to highly variable, and sometimes inconsistent results. The main objective of this study is to bring light into the handling of sputum samples to establish a standardised and robust protocol before rheological measurements. Sputum collected from 22 CF and 10 NCFB adults, was divided into control (vortexed and fresh: non-heated and non-frozen) and three treated conditions (either non-vortexed, heated or frozen). In addition, 6 CF expectorations were used to study the dynamics of ageing over 24 h. Sputum's mechanical properties were measured with a rotational rheometer to obtain their properties at rest, elastic ([Formula: see text]) and viscous moduli ([Formula: see text]), and at the onset of flow, critical deformation ([Formula: see text]) and critical stress ([Formula: see text]). We demonstrate that heating sputum is completely destructive while freezing sputa at [Formula: see text] has no discernible effect on their rheology. We also show that the variability of rheological measurements largely resulted from the sample's macroscopic heterogeneity, and can be greatly reduced by non-destructive vortex homogenisation. Finally, we observed contrasted ageing effects as a fonction of purulence: while the viscoelasticity of purulent samples reduced by half within 6 h after collection, semi-purulent samples did not evolve. These results guide towards a robust unified protocol for simple sputum handling in rheometry. We therefore suggest to vortex and snap freeze sputum samples immediately after collection when direct testing is not possible.
Topics: Adult; Humans; Sputum; Cystic Fibrosis; Rheology; Bronchiectasis; Lung Diseases, Obstructive
PubMed: 37169792
DOI: 10.1038/s41598-023-34043-9 -
BMJ Clinical Evidence Jul 2015Acute bronchitis affects more than 40 in 1000 adults per year in the UK. The causes are usually considered to be infective, but only around half of people have... (Review)
Review
INTRODUCTION
Acute bronchitis affects more than 40 in 1000 adults per year in the UK. The causes are usually considered to be infective, but only around half of people have identifiable pathogens. The role of smoking or of environmental tobacco smoke inhalation in predisposing to acute bronchitis is unclear. One third of people may have longer-term symptoms or recurrence.
METHODS AND OUTCOMES
We conducted a systematic review, aiming to answer the following clinical question: What are the effects of treatments for acute bronchitis in people without chronic respiratory disease? We searched: Medline, Embase, The Cochrane Library, and other important databases up to May 2015 (Clinical Evidence overviews are updated periodically; please check our website for the most up-to-date version of this overview).
RESULTS
At this update, searching of electronic databases retrieved 420 studies. After deduplication and removal of conference abstracts, 306 records were screened for inclusion in the overview. Appraisal of titles and abstracts led to the exclusion of 245 studies and the further review of 61 full publications. Of the 61 full articles evaluated, three updated systematic reviews and three RCTs were added at this update. We performed a GRADE evaluation for 12 PICO combinations.
CONCLUSIONS
In this systematic review we categorised the efficacy for six intervention-comparison combinations, based on information about the effectiveness and safety of the following interventions: antibiotics, antihistamines, antitussives, beta2 agonists (inhaled), and expectorants/mucolytics.
Topics: Acute Disease; Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Anti-Bacterial Agents; Antitussive Agents; Bronchitis; Expectorants; Histamine Antagonists; Humans; Treatment Outcome
PubMed: 26186368
DOI: No ID Found -
Molecules (Basel, Switzerland) Jan 2022Naringenin (NRG) is a natural flavonoid compound abundantly present in citrus fruits and has the potential to treat respiratory disorders. However, the clinical...
Naringenin (NRG) is a natural flavonoid compound abundantly present in citrus fruits and has the potential to treat respiratory disorders. However, the clinical therapeutic effect of NRG is limited by its low bioavailability due to poor solubility. To enhance the solubility, naringenin nanosuspensions (NRG-NSps) were prepared by applying tocopherol polyethylene glycol succinate (TPGS) as the nanocarrier via the media-milling method. The particle size, morphology, and drug-loading content of NRG-NSps were examined, and the stability was evaluated by detecting particle size changes in different physiological media. NRG-NSps exhibited a flaky appearance with a mean diameter of 216.9 nm, and the drug-loading content was 66.7%. NRG-NSps exhibited good storage stability and media stability. NRG-NSps presented a sustainable release profile, and the cumulative drug-release rate approached approximately 95% within 7 d. NRG-NSps improved the antitussive effect significantly compared with the original NRG, the cough frequency was decreased from 22 to 15 times, and the cough incubation period was prolonged from 85.3 to 121.6 s. Besides, NRG-NSps also enhanced expectorant effects significantly, and phenol red secretion was increased from 1.02 to 1.45 μg/mL. These results indicate that NRG-NSps could enhance the bioavailability of NRG significantly and possess a potential clinical application.
Topics: Animals; Antitussive Agents; Biological Availability; Cough; Disease Models, Animal; Drug Delivery Systems; Drug Evaluation, Preclinical; Drug Liberation; Expectorants; Flavanones; Mice; Nanoparticles; Particle Size; Solubility; Suspensions
PubMed: 35164006
DOI: 10.3390/molecules27030741 -
Respiratory Research May 2019To date there are no head-to-head studies comparing different mucolytic/antioxidant agents. Considering the inconsistent evidence resulting from the pivotal studies on... (Comparative Study)
Comparative Study Meta-Analysis
Efficacy and safety profile of mucolytic/antioxidant agents in chronic obstructive pulmonary disease: a comparative analysis across erdosteine, carbocysteine, and N-acetylcysteine.
BACKGROUND
To date there are no head-to-head studies comparing different mucolytic/antioxidant agents. Considering the inconsistent evidence resulting from the pivotal studies on mucolytic/antioxidant agents tested in chronic obstructive pulmonary disease (COPD), and the recent publication of Reducing Exacerbations and Symptoms by Treatment with ORal Erdosteine in COPD (RESTORE) study, we have performed a meta-analysis to compare the efficacy and safety of erdosteine 600 mg/day, carbocysteine 1500 mg/day, and N-acetylcysteine (NAC) 1200 mg/day in COPD.
METHODS
A pairwise and network meta-analyses were performed to assess the efficacy of erdosteine, carbocysteine, and NAC on acute exacerbation of COPD (AECOPD), duration of AECOPD, and hospitalization. The frequency of adverse events (AEs) was also investigated.
RESULTS
Data obtained from 2753 COPD patients were extracted from 7 RCTs published between 2004 and 2017. In the pairwise meta-analysis mucolytic/antioxidant agents significantly reduced the risk of AECOPD (RR 0.74 95%CI 0.68-0.80). The network meta-analysis provided the following rank of effectiveness: erdosteine>carbocysteine>NAC. Only erdosteine reduced the risk of experiencing at least one AECOPD (P < 0.01) and the risk of hospitalization due to AECOPD (P < 0.05). Erdosteine and NAC both significantly reduced the duration of AECOPD (P < 0.01). The AEs induced by erdosteine, carbocysteine, and NAC were mild in severity and generally well tolerated. The quality of evidence of this quantitative synthesis is moderate.
CONCLUSIONS
The overall efficacy/safety profile of erdosteine is superior to that of both carbocysteine and NAC. Future head-to-head studies performed on the same COPD populations are needed to definitely confirm the results of this meta-analysis.
TRIAL REGISTRATION
CRD42016053762 .
Topics: Acetylcysteine; Antioxidants; Carbocysteine; Expectorants; Humans; Pulmonary Disease, Chronic Obstructive; Randomized Controlled Trials as Topic; Thioglycolates; Thiophenes; Treatment Outcome
PubMed: 31133026
DOI: 10.1186/s12931-019-1078-y -
European Respiratory Review : An... Jun 2010Mucus hypersecretion is a clinical feature of severe respiratory diseases such as asthma, cystic fibrosis and chronic obstructive pulmonary disease. Airway mucosal... (Review)
Review
Mucus hypersecretion is a clinical feature of severe respiratory diseases such as asthma, cystic fibrosis and chronic obstructive pulmonary disease. Airway mucosal infection and/or inflammation associated with these diseases often gives rise to inflammatory products, including neutrophil-derived DNA and filamentous actin, in addition to bacteria, apoptotic cells and cellular debris, that may collectively increase mucus production and viscosity. Mucoactive agents have been the medication of choice for the treatment of respiratory diseases in which mucus hypersecretion is a clinical complication. The main purpose of mucoactive drugs is to increase the ability to expectorate sputum and/or decrease mucus hypersecretion. Many mucoactive drugs are currently available and can be classified according to their putative mechanism of action. Mucoactive medications include expectorants, mucoregulators, mucolytics and mucokinetics. By developing our understanding of the specific effects of mucoactive agents, we may result in improved therapeutic use of these drugs. The present review provides a summary of the most clinically relevant mucoactive drugs in addition to their potential mechanism of action.
Topics: Expectorants; Humans; Mucus; Pulmonary Disease, Chronic Obstructive
PubMed: 20956181
DOI: 10.1183/09059180.00003510 -
Pharmaceutical Biology Dec 2021(KOG) is a traditional mixed herb preparation consisting of CA Meyer (Araliaceae), Wolf (Polyporaceae), (Gaertner) Liboschitz ex Steudel (Orobanchaceae), and honey....
CONTEXT
(KOG) is a traditional mixed herb preparation consisting of CA Meyer (Araliaceae), Wolf (Polyporaceae), (Gaertner) Liboschitz ex Steudel (Orobanchaceae), and honey. Various pharmacological effects of KOG are reported, but the efficacy on respiratory diseases has not been evaluated.
OBJECTIVE
The anti-inflammatory, expectorant, and antitussive properties of KOG were examined using animal models of respiratory diseases.
MATERIALS AND METHODS
KOG (100, 200, and 400 mg/kg) was orally administered to ICR mice ( = 8) once a day for 11 days. Anti-inflammatory effects of vehicle, xylene, KOG and DEXA (1 mg/kg) were determined by monitoring edoema and redness of treated ears, and measuring the relative and absolute weight of each ear. Expectorant properties of vehicle, KOG and AM (250 mg/kg) were evaluated by observing body surface redness, and the amount of mucous secreted by the trachea. The antitussive potential of vehicle, NHOH, KOG and TB (50 mg/kg) was evaluated by monitoring changes in the number of coughs (for 6 min).
RESULTS
KOG (400 mg/kg) treated mice showed 31.29% and 30.72% ( < 0.01) decreases in the relative and absolute weights of each ear relative to xylene control mice, 39.06% increases ( < 0.01) in TLF OD values relative to intact vehicle control mice, and 59.53% decrease ( < 0.01) in coughing compared to NHOH control mice. Dose-dependent changes were observed in all experimental models.
CONCLUSIONS
KOG may be a potential therapeutic agent for the treatment of various respiratory diseases, particularly those caused by environmental toxins.
Topics: Administration, Oral; Animals; Anti-Inflammatory Agents; Antitussive Agents; Cough; Disease Models, Animal; Dose-Response Relationship, Drug; Expectorants; Inflammation; Male; Mice; Mice, Inbred ICR; Phytotherapy; Plant Extracts
PubMed: 33770452
DOI: 10.1080/13880209.2021.1892155 -
Yonsei Medical Journal May 2015This study aims to investigate the additive effect of the Hedera helix (HH) and Rhizoma coptidis (RC) extracts mixture on antitussive and expectorant activities in...
PURPOSE
This study aims to investigate the additive effect of the Hedera helix (HH) and Rhizoma coptidis (RC) extracts mixture on antitussive and expectorant activities in animals.
MATERIALS AND METHODS
The expectorant assay was performed with phenol red secretion in mice trachea. Mice or guinea pigs were randomly divided into groups of 8 each, including negative and positive control groups. After gastric administration of the test extracts in mice, 2.5% phenol red solution (0.2 mL) was intraperitoneally injected. Trachea was dissected and optical density of tracheal secretion was measured. After gastric administration of the test extracts in guinea pigs, the antitussive activities were assessed using a citric acid-induced cough measurement.
RESULTS
The extracts of HH and RC significantly increased tracheal secretion and inhibited cough. The mixture of HH and RC extracts in a 1:1 concentration at a dose of 200 mg/kg showed a more potent effect on phenol red secretion (25.25±3.14) and cough inhibition (61.25±5.36) than the individual use of each extracts [phenol red secretion; HH 13.39±4.22 (p=0.000), RC 20.78±2.50 (p=0.010), cough inhibition; HH 9.89±4.14 (p=0.010), RC 30.25±7.69 (p=0.000)]. A 3:1 ratio mixture of HH to RC demonstrated an optimal expectorant effect (p<0.001), and this mixture showed expectorant and antitussive effects in a dose-dependent manner.
CONCLUSION
This study provides evidence for antitussive and expectorant effect of a 3:1 mixture of HH and RC, which may be a useful therapeutic option for respiratory diseases.
Topics: Animals; Antitussive Agents; Behavior, Addictive; Coptis chinensis; Cough; Drugs, Chinese Herbal; Ethanol; Expectorants; Guinea Pigs; Hedera; Male; Mice; Phytotherapy; Plant Extracts; Plant Roots; Trachea
PubMed: 25837191
DOI: 10.3349/ymj.2015.56.3.819 -
The Cochrane Database of Systematic... May 2014Bronchiectasis is predominantly an acquired disease process that represents the end stage of a variety of unrelated pulmonary insults. It is defined as persistent... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Bronchiectasis is predominantly an acquired disease process that represents the end stage of a variety of unrelated pulmonary insults. It is defined as persistent irreversible dilatation and distortion of medium-sized bronchi. It has been suggested that with widespread use of high-resolution computed tomography, more bronchiectasis diagnoses are being made. Patients diagnosed with bronchiectasis frequently have difficulty expectorating sputum. Sputum therefore is retained in the lungs and may become infected, leading to further lung damage. Mucolytic agents target hypersecretion or changed physiochemical properties of sputum to make it easier to clear. One drug, recombinant human DNase, breaks down the DNA that is released at the site of infection by neutrophils.Mucus clearance along with antimicrobial therapy remains an integral part of bronchiectasis management. Chest physiotherapy along with mucolytic agents is commonly used in practice without clear supportive evidence.
OBJECTIVES
To determine whether ingested or inhaled mucolytics are effective in the treatment of patients with bronchiectasis.
SEARCH METHODS
We searched the Cochrane Airways Group Specialised Register and reference lists of relevant articles. We contacted experts in the field and drug companies. Searches were current as of June 2013.
SELECTION CRITERIA
Randomised trials of mucolytic treatment in people with bronchiectasis but not cystic fibrosis.
DATA COLLECTION AND ANALYSIS
Data extraction was performed independently by two review authors. Study authors were contacted for confirmation.
MAIN RESULTS
Four trials (with a combined total of 528 adult participants) were included, but almost none of the data from these studies could be aggregated in a meta-analysis.One trial (with 88 participants) compared bromhexine versus placebo. Compared with placebo, high doses of bromhexine with antibiotics eased difficulty in expectoration (mean difference (MD) -0.53, 95% confidence interval (CI) -0.81 to -0.25 at 16 days); the quality of the evidence was rated as low. A reduction in sputum production was noted with bromhexine (MD -21.5%, 95% CI -38.9 to -4.1 at day 16); again the quality of the evidence was rated as low. No significant differences between bromhexine and placebo were observed with respect to reported adverse events (odds ratio (OR) 2.93; 95% CI 0.12 to 73.97), and again the quality of the evidence was rated as low.In a single small, blinded but not placebo-controlled trial of older (> 55 years) participants with stable bronchiectasis and mucus hypersecretion, erdosteine combined with physiotherapy over a 15-day period improved spirometry and sputum purulence more effectively compared with physiotherapy alone. The spirometric improvement was small (MD 200 mL in forced expiratory volume in one second (FEV1) and 300 mL in forced vital capacity (FVC)) and was apparent only at day 15, not at earlier time points.The remaining two studies (with a combined total of 410 participants) compared recombinant human DNase (RhDNase) versus placebo. These two studies were very different (one was a two-week study of 61 participants, and the other ran for 24 weeks and included 349 participants), and the opportunity for combining data from the two studies was very limited. Compared with placebo, recombinant human DNase showed no difference in FEV1 or FVC in the smaller study but showed a significant negative effect on FEV1 in the larger and longer study. For reported adverse events, no significant differences between recombinant human DNase and placebo were noted. In all of the above comparisons of recombinant human DNase versus placebo, the quality of the evidence was judged to be low.
AUTHORS' CONCLUSIONS
Given the harmful effects of recombinant human DNase in one trial and no evidence of benefit, this drug should be avoided in non-cystic fibrosis bronchiectasis, except in the context of clinical trials. Evidence is insufficient to permit evaluation of the routine use of other mucolytics for bronchiectasis. High doses of bromhexine coupled with antibiotics may help with sputum production and clearance, but long-term data and robust clinical outcomes are lacking. Similarly, erdosteine may be a useful adjunct to physiotherapy in stable patients with mucus hypersecretion, but robust longer-term trials are required.Generally, clinical trials in children on the use of various mucolytic agents are lacking. As the number of agents available on the market, such as RhDNase, acetylcysteine and bromhexine, is increasing, improvement of the evidence base is needed.
Topics: Anti-Bacterial Agents; Bromhexine; Bronchiectasis; Deoxyribonucleases; Drug Therapy, Combination; Expectorants; Humans; Randomized Controlled Trials as Topic; Recombinant Proteins; Thioglycolates; Thiophenes
PubMed: 24789119
DOI: 10.1002/14651858.CD001289.pub2 -
European Review For Medical and... Jun 2023Evidence for the mucolytic and expectorant efficacy of intravenous (IV) N-acetylcysteine (NAC) is limited. This study aimed to evaluate in a large, multicenter,... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
Evidence for the mucolytic and expectorant efficacy of intravenous (IV) N-acetylcysteine (NAC) is limited. This study aimed to evaluate in a large, multicenter, randomized, controlled, subject, and rater-blinded study whether IV NAC is superior to placebo and non-inferior to ambroxol in improving sputum viscosity and expectoration difficulty.
PATIENTS AND METHODS
A total of 333 hospitalized subjects from 28 centers in China with respiratory disease (such as acute bronchitis, chronic bronchitis and exacerbations, emphysema, mucoviscidosis, and bronchiectasis) and abnormal mucus secretion were randomly allocated in a 1:1:1 ratio to receive NAC 600 mg, ambroxol hydrochloride 30 mg, or placebo as an IV infusion twice daily for 7 days. Mucolytic and expectorant efficacy was assessed by ordinal categorical 4-point scales and analyzed by stratified and modified Mann-Whitney U statistics.
RESULTS
NAC showed consistent and statistically significant superiority to placebo and non-inferiority to ambroxol in change from baseline to day 7 in both sputum viscosity scores [mean (SD) difference 0.24 (0.763), p<0.001 vs. placebo] and expectoration difficulty score [mean (SD) difference 0.29 (0.783), p=0.002 vs. placebo]. Safety findings confirm the good tolerability profile of IV NAC reported from previous small studies, and no new safety concerns were identified.
CONCLUSIONS
This is the first large, robust study of the efficacy of IV NAC in respiratory diseases with abnormal mucus secretion. It provides new evidence for IV NAC administration in this indication in clinical situations where the IV route is preferred.
Topics: Humans; Acetylcysteine; Expectorants; Ambroxol; Respiration Disorders; Mucus; Double-Blind Method
PubMed: 37318485
DOI: 10.26355/eurrev_202306_32628 -
Chest Aug 2015Cystic fibrosis (CF) is the most common life-limiting inherited illness of whites. Most of the morbidity and mortality in CF stems from impaired mucociliary clearance... (Review)
Review
Cystic fibrosis (CF) is the most common life-limiting inherited illness of whites. Most of the morbidity and mortality in CF stems from impaired mucociliary clearance leading to chronic, progressive airways obstruction and damage. Significant progress has been made in the care of patients with CF, with advances focused on improving mucociliary clearance, minimizing inflammatory damage, and managing infections; these advances include new antimicrobial therapies, mucolytic and osmotic agents, and antiinflammatory treatments. More recently, researchers have targeted disease-causing mutations using therapies to promote gene transcription and improve channel function, which has led to impressive physiologic changes in some patients. As we develop more advanced, allele-directed therapies for the management of CF, it will become increasingly important to understand the specific genetic and environmental interactions that cause the significant heterogeneity of lung disease seen in the CF population. This understanding of CF endotypes will allow for more targeted, personalized therapies for future patients. This article reviews the genetic and molecular basis of CF lung disease, the treatments currently available, and novel therapies that are in development.
Topics: Anti-Bacterial Agents; Anti-Inflammatory Agents; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Expectorants; Genetic Therapy; Humans; Molecular Targeted Therapy; Primary Prevention
PubMed: 25764168
DOI: 10.1378/chest.14-1997