Over the past thirty years, research has shown the huge potential of chitosan in biomedical applications such as drug delivery, tissue engineering and regeneration, cancer therapy, and antimicrobial ...treatments, among others. One of the major advantages of this interesting polysaccharide is its modifiability, which facilitates its use in tailor-made applications. In this way, the molecular structure of chitosan has been conjugated with multiple molecules to modify its mechanical, biological, or chemical properties. Here, we review the conjugation of chitosan with some bioactive molecules: hydroxycinnamic acids (HCAs); since these derivatives have been probed to enhance some of the biological effects of chitosan and to fine-tune its characteristics for its application in the biomedical field. First, the main characteristics of chitosan and HCAs are presented; then, the currently employed conjugation strategies between chitosan and HCAs are described; and, finally, the studied biomedical applications of these derivatives are discussed to present their limitations and advantages, which could lead to proximal therapeutic uses.
Mucous exudates occluding the lumen of small airways are associated with reduced lung function and mortality in subjects with COPD; however, luminal plugs in large airways have not been widely ...studied. We aimed to examine the associations of chest CT scan-identified luminal plugging with lung function, health-related quality of life, and COPD phenotypes.
We randomly selected 100 smokers without COPD and 400 smokers with COPD from the COPDGene Study. Luminal plugging was visually identified on inspiratory CT scans at baseline and 5-year follow-up. The relationships of luminal plugging to FEV
, St. George's Respiratory Questionnaire (SGRQ) score, emphysema on CT scan (defined as the percentage of low attenuation area < 950 Hounsfield units %LAA-950), and chronic bronchitis were assessed using linear and logistic multivariable analyses.
Overall, 111 subjects (22%) had luminal plugging. The prevalence of luminal plugging was higher in subjects with COPD than those without COPD (25% vs 10%, respectively; P = .001). In subjects with COPD, luminal plugging was significantly associated with FEV
% predicted (estimate, -6.1; SE, 2.1; P = .004) and SGRQ score (estimate, 4.9; SE, 2.4; P = .04) in adjusted models. Although luminal plugging was associated with log %LAA-950 (estimate, 0.43; SE, 0.16; P = .007), its relationship with chronic bronchitis did not reach statistical significance (P = .07). Seventy-three percent of subjects with COPD with luminal plugging at baseline had it 5 years later.
In subjects with COPD, CT-identified luminal plugging is associated with airflow obstruction, worse health-related quality of life, and emphysema phenotype. This imaging feature may supplement the current clinical assessment of chronic mucus hypersecretion in COPD.
Exposure to cigarette smoke has been shown to lead to vascular remodelling. Computed tomography (CT) imaging measures of vascular pruning have been associated with pulmonary vascular disease, an ...important morbidity associated with smoking. In this study we compare CT-based measures of distal vessel loss to histological vascular and parenchymal changes.
A retrospective review of 80 patients who had undergone lung resection identified patients with imaging appropriate for three-dimensional (3D) vascular reconstruction (n=18) and a second group for two-dimensional (2D) analysis (n=19). Measurements of the volume of the small vessels (3D) and the cross-sectional area of the small vessels (<5 mm
cross-section) were computed. Histological measures of cross-sectional area of the vasculature and loss of alveoli septa were obtained for all subjects.
The 2D cross-sectional area of the vasculature on CT imaging was associated with the histological vascular cross-sectional area (r=0.69; p=0.001). The arterial small vessel volume assessed by CT correlated with the histological vascular cross-sectional area (r=0.50; p=0.04), a relationship that persisted even when adjusted for CT-derived measures of emphysema in a regression model.
Loss of small vessel volume in CT imaging of smokers is associated with histological loss of vascular cross-sectional area. Imaging-based quantification of pulmonary vasculature provides a noninvasive method to study the multiscale effects of smoking on the pulmonary circulation.
Discovering airway gene expression alterations associated with radiological bronchiectasis may improve the understanding of the pathobiology of early-stage bronchiectasis.
Presence of radiological ...bronchiectasis in 173 individuals without a clinical diagnosis of bronchiectasis was evaluated. Bronchial brushings from these individuals were transcriptomically profiled and analysed. Single-cell deconvolution was performed to estimate changes in cellular landscape that may be associated with early disease progression.
20 participants have widespread radiological bronchiectasis (three or more lobes). Transcriptomic analysis reflects biological processes associated with bronchiectasis including decreased expression of genes involved in cell adhesion and increased expression of genes involved in inflammatory pathways (655 genes, false discovery rate <0.1, log
fold-change >0.25). Deconvolution analysis suggests that radiological bronchiectasis is associated with an increased proportion of ciliated and deuterosomal cells, and a decreased proportion of basal cells. Gene expression patterns separated participants into three clusters: normal, intermediate and bronchiectatic. The bronchiectatic cluster was enriched by participants with more lobes of radiological bronchiectasis (p<0.0001), more symptoms (p=0.002), higher SERPINA1 mutation rates (p=0.03) and higher computed tomography derived bronchiectasis scores (p<0.0001).
Genes involved in cell adhesion, Wnt signalling, ciliogenesis and interferon-γ pathways had altered expression in the bronchus of participants with widespread radiological bronchiectasis, possibly associated with decreased basal and increased ciliated cells. This gene expression pattern is not only highly enriched among individuals with radiological bronchiectasis, but also associated with airway-related symptoms in those without discernible radiological bronchiectasis, suggesting that it reflects a bronchiectasis-associated, but non-bronchiectasis-specific lung pathophysiological process.
Summary
Aims
Non‐cystic fibrosis bronchiectasis (NCFB) is a chronic, progressive respiratory disorder characterised by irreversibly and abnormally dilated airways, persistent cough, excessive sputum ...production and recurrent pulmonary infections. In the last several decades, its prevalence has increased, making it likely to be encountered in the primary care setting. The aim was to review the clinical presentation and diagnosis of NCFB, with an emphasis on the role of computed tomography (CT).
Methods
For this review, trials and reports were identified from PubMed/Medline and ClinicalTrials.gov from the US NIH and the Cochrane Register of Controlled Trials. The search used keywords: bronchiectasis, non‐cystic fibrosis bronchiectasis, chronic pulmonary infection and computed tomography. No date/language restrictions were used.
Results
Non‐cystic fibrosis bronchiectasis often coexists with other respiratory conditions, such as chronic obstructive pulmonary disease. The prevalence of NCFB is increasing, particularly in women and older individuals, possibly as a result of increased physician awareness and widespread use of CT, which is the gold standard for the diagnosis of NCFB. CT can assist in identifying an underlying cause of NCFB and determining the extent and severity of the disease.
Discussion
Non‐cystic fibrosis bronchiectasis should be suspected in the primary care setting in patients with chronic cough, purulent sputum and frequent respiratory infections that tend to resolve slowly or partially. Early diagnosis and determination of the extent and severity of the disease by CT and other tests are critical to establish therapy to improve quality of life and potentially slow progressive decline of lung function in patients with NCFB.
Aging is associated with reduced FEV
to FVC ratio (FEV
/FVC), hyperinflation, and alveolar enlargement, but little is known about how age affects small airways.
To determine if chest computed ...tomography (CT)-assessed functional small airway would increase with age, even among asymptomatic individuals.
We used parametric response mapping analysis of paired inspiratory/expiratory CTs to identify functional small airway abnormality (PRM
) and emphysema (PRM
) in the SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study) cohort. Using adjusted linear regression models, we analyzed associations between PRM
and age in subjects with or without airflow obstruction. We subdivided participants with normal spirometry based on respiratory-related impairment (6-minute-walk distance <350 m, modified Medical Research Council ≥2, chronic bronchitis, St. George's Respiratory Questionnaire >25, respiratory events requiring treatment antibiotics and/or steroids or hospitalization in the year before enrollment).
Among 580 never- and ever-smokers without obstruction or respiratory impairment, PRM
increased 2.7% per decade, ranging from 3.6% (ages 40-50 yr) to 12.7% (ages 70-80 yr). PRM
increased nonsignificantly (0.1% ages 40-50 yr to 0.4% ages 70-80 yr; P = 0.34). Associations were similar among nonobstructed individuals with respiratory-related impairment. Increasing PRM
in subjects without airflow obstruction was associated with increased FVC (P = 0.004) but unchanged FEV
(P = 0.94), yielding lower FEV
/FVC ratios (P < 0.001). Although emphysema was also significantly associated with lower FEV
/FVC (P = 0.04), its contribution relative to PRM
in those without airflow obstruction was limited by its low burden.
In never- and ever-smokers without airflow obstruction, aging is associated with increased FVC and CT-defined functional small airway abnormality regardless of respiratory symptoms.
The present review aims to summarize the most recent evidence related to imaging and severe asthma, both with regard to advances in imaging research and to their current and potential clinical ...implications.
Recent work in imaging in severe asthma has principally been using computed tomography (CT) and MRI, as well as the integration of the two. Some of the most notable findings include the use of CT imaging biomarkers to create unique clusters of asthmatics, and the use of co-registration to link CT images of airways with regional variation in ventilation in MRI. In addition, temporal studies have shown that some the ventilation defects found using MRI in asthmatics are intermittent and others are persistent, but both are associated with lower lung function.
The role of imaging in severe asthma currently is primarily in the exclusion of comorbid or other conditions, or in the assessment for complications in the setting of acute decompensation. A rapidly expanding body of literature using CT and MRI suggests that these tools may soon be of utility in the chronic management of the disease.
Few sclerophyllous plants from the central coast of Chile have been systematically studied. This work describes the phytochemical composition and antimicrobial properties of
Pers. (sin.
), a shrub ...found in the first line and near the Pacific coast.
has been traditionally used by indigenous inhabitants of today's central Chile for its medicinal properties. Few reports exist regarding the phytochemistry characterization and biological activities of
. A hydroalcoholic extract of
was prepared from leaves and small branches. Qualitative phytochemical characterization indicated the presence of alkaloids, steroids, terpenoids, flavonoids, phenolic, and tannin compounds. The antimicrobial activity of this extract was assessed in a panel of microorganisms including Gram-positive bacteria, Gram-negative bacteria, and pathogenic yeasts. The extract displayed an important antimicrobial effect against Gram-positive bacteria,
and
but not against Gram-negatives, for which an intact Lipopolysaccharide is apparently the determinant of resistance to
extracts. The hydroalcoholic extract was then fractionated through a Sephadex LH-20/methanol-ethyl acetate column. Afterward, the fractions were pooled according to a similar pattern visualized by TLC/UV analysis. Fractions obtained by this criterion were assessed for their antimicrobial activity against
. The fraction presenting the most antimicrobial activity was HPLC-ESI-MS/MS, obtaining molecules related to caffeoylquinic acid, dicaffeoylquinic acid, and quercetin, among others. In conclusion, the extracts of
showed strong antimicrobial activity, probably due to the presence of metabolites derived from phenolic acids, such as caffeoylquinic acid, and flavonoids, such as quercetin, which in turn could be responsible for helping with wound healing. In addition, the development of antimicrobial therapies based on the molecules found in
could help to combat infection caused by pathogenic yeasts and Gram-positive bacteria, without affecting the Gram-negative microbiota.
PDF
