Novel approaches for drug delivery systems in nanomedicine: effects of particle design and shape.

Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2011 Dec 2;

Authors: Daum N, Tscheka C, Neumeyer A, Schneider M

Abstract
The identification of novel drug candidates for the treatment of diseases like cancer, infectious diseases, or allergies (especially asthma) assigns new tasks for pharmaceutical technology. With respect to drug delivery several problems occur such as low solubility and hence low bioavailability or restriction to inconvenient routes of administration. Nanotechnological approaches promise to circumvent some of these problems, therefore being well suited for future applications as nanomedicines. Furthermore, efficient and sufficient loading is a critical issue that is approached through mesoporous particles and/or through nonspherical particles both offering larger volumes and surfaces. Special interest is laid on the effect of shape of particulate materials on the body and related physiological mechanisms. The modified response of biological systems on different shapes opens a new dimension to adjust particle system interaction. Finally, the biological response to these systems will determine the fate with respect to their therapeutic value. Therefore, the interaction pattern between nonspherical particulate materials and biological systems as well as the production processes are highlighted. WIREs Nanomed Nanobiotechnol 2011. doi: 10.1002/wnan.165 For further resources related to this article, please visit the WIREs website.

PMID: 22140017 [PubMed - as supplied by publisher]

Wheeze in preschool age is associated with pulmonary bacterial infection and resolves after antibiotic therapy.

PLoS One. 2011;6(11):e27913

Authors: Schwerk N, Brinkmann F, Soudah B, Kabesch M, Hansen G

Abstract
BACKGROUND: Neonates with airways colonized by Haemophilus influenzae, Streptococcus pneumoniae or Moraxella catarrhalis are at increased risk for recurrent wheeze which may resemble asthma early in life. It is not clear whether chronic colonization by these pathogens is causative for severe persistent wheeze in some preschool children and whether these children might benefit from antibiotic treatment. We assessed the relevance of bacterial colonization and chronic airway infection in preschool children with severe persistent wheezing and evaluated the outcome of long-time antibiotic treatment on the clinical course in such children.
METHODOLOGY/PRINCIPAL FINDINGS: Preschool children (n = 42) with severe persistent wheeze but no symptoms of acute pulmonary infection were investigated by bronchoscopy and bronchoalveolar lavage (BAL). Differential cell counts and microbiological and virological analyses were performed on BAL samples. Patients diagnosed with bacterial infection were treated with antibiotics for 2-16 weeks (n = 29). A modified ISAAC questionnaire was used for follow-up assessment of children at least 6 months after bronchoscopy. Of the 42 children with severe wheezing, 34 (81%) showed a neutrophilic inflammation and 20 (59%) of this subgroup had elevated bacterial counts (≥10(4) colony forming units per milliliter) suggesting infection. Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis were the most frequently isolated species. After treatment with appropriate antibiotics 92% of patients showed a marked improvement of symptoms upon follow-up examination.
CONCLUSIONS/SIGNIFICANCE: Chronic bacterial infections are relevant in a subgroup of preschool children with persistent wheezing and such children benefit significantly from antibiotic therapy.

PMID: 22140482 [PubMed - in process]

The presence of pepsin in the lung and its relationship to pathologic gastro-esophageal reflux.

Neurogastroenterol Motil. 2011 Dec 5;

Authors: Rosen R, Johnston N, Hart K, Khatwa U, Nurko S

Abstract
Background  Pepsin has been proposed as a biomarker of reflux-related lung disease. The goal of this study was to determine (i) if there is a higher reflux burden as measured by pH-MII in patients that are pepsin positive in the lung, and (ii) the sensitivity of pepsin in predicting pathologic reflux by pH, MII, and EGD. Methods  We recruited children between the ages of 1-21 with chronic cough or asthma undergoing bronchoscopy, esophagogastroduodenoscopy (EGD), and multichannel intraluminal impedance (pH-MII) probe placement. The reflux profiles were compared between those patients who were pepsin positive and negative; proportions were compared using Chi-squared analyses and means were compared using t-testing. Key Results  Only the mean number of non-acid reflux events was associated with pepsin positivity (0.04). The sensitivity and specificity of pepsin in predicting pathologic reflux by pH-MII or EGD was 57% and 65%, respectively. The positive predictive value of pepsin in predicting pathologic reflux by pH, MII or EGD was 50% (11/22), and the negative predictive value was 71% (20/28). There was a significantly higher mean LLMI in patients who were pepsin positive compared with pepsin negative patients (81 ± 54 vs 47 ± 26, P = 0.001). Conclusions & Inferences  Lung pepsin cannot predict pathologic reflux in the esophagus, but its correlation with lung inflammation suggests that pepsin may be an important biomarker for reflux-related lung disease.

PMID: 22141343 [PubMed - as supplied by publisher]

Asthma phenotypes: consistency of classification using induced sputum.

Respirology. 2011 Dec 5;

Authors: Hancox RJ, Cowan DC, Aldridge RE, Cowan JO, Palmay R, Williamson A, Town GI, Taylor DR

Abstract
SUMMARY AT A GLANCE: The stability of the classification of asthma phenotypes was studied in two clinical trials. Participants' sputum frequently changed between eosinophilic and non-eosinophilic inflammation. These changes occurred both spontaneously and in response to treatment. A diagnosis of non-eosinophilic, asthma should not be based on a single sputum sample. ABSTRACT: Background and Objective.  Asthma can be classified as eosinophilic or non-eosinophilic based on the cell profile of induced sputum. This classification can help to determine whether corticosteroid treatment is indicated. We assessed the stability of these phenotypes over time and with different treatment regimens. Methods.  Clinically stable, non-smoking, asthmatic adults were enrolled in one of two studies. In study one, induced sputum cell counts from 28 subjects were analysed after four weeks without corticosteroid treatment and after 6 week treatments with placebo, regular inhaled beta-agonist, inhaled corticosteroid, and combined beta-agonist and corticosteroid. In study two, sputum from 26 subjects with non-eosinophilic asthma was analysed after 12 weeks of placebo and after four 2-week corticosteroid washouts. Sputum with < 2% eosinophils was classified as non-eosinophilic. Results.  Sputum classification changed frequently in both studies. In study one, only one of 8 participants with non-eosinophilic sputum after placebo treatment remained non-eosinophilic throughout. In study two, all of participants had at least one eosinophilic sputum sample, despite the fact that all had been non-eosinophilic at recruitment. Neutrophilic asthma was uncommon in both studies and was also inconsistent. Conclusions.  The phenotypic classification of asthma changes frequently. A diagnosis of non-eosinophilic asthma should not be based on a single sputum sample.

PMID: 22142406 [PubMed - as supplied by publisher]