Related Articles

Back to the future: Inhaled drug products.

J Pharm Sci. 2013 Feb 4;

Authors: Hickey AJ

Abstract
Inhaled therapeutic aerosols continue to be an important treatment for asthma and pulmonary diseases. A variety of dosage forms are employed for different indications and demographics including pressurized or propellant-driven metered dose inhalers, dry powder inhalers, and nebulizers/nebules. Research and development in this field has shown remarkable innovation in the past decade. Important new drug products for the treatment of asthma, chronic obstructive pulmonary disease, cystic fibrosis, diabetes, and a range of neurological disorders have been developed. New devices in each of the dosage form categories also have been developed, and new formulation technologies have been adopted. Unlike many other dosage forms, as new inhaled products appeared few of the existing products were converted to generic form. This may be explained by the formulation and device complexity, the implications for degree of difficulty in obtaining regulatory approval, and the prevalence of intellectual property in the field. After the setback of the initial approval and subsequent withdrawal of the Exubera®-inhaled insulin, there appeared to be reluctance to consider the pulmonary route of administration for systemically acting agents, particularly peptides and proteins. However, recent product development activities and approvals suggest that attitudes may be changing in favor of systemic delivery following inhaled aerosol administration. The new inhaled drug technologies seem to be driving reconsideration of therapeutic categories for indications that were of interest at the inception of modern inhaled drug therapy in the past century. We should embrace the opportunity to use new drugs and technologies to go back to the future! © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci.

PMID: 23381932 [PubMed - as supplied by publisher]

Integrated care model with self-management in chronic obstructive pulmonary disease: From family physicians to specialists.

Chron Respir Dis. 2013 Feb 4;

Authors: Bourbeau J, Saad N

Abstract
Patient with chronic obstructive pulmonary disease (COPD) has to become a partner and an active participant in his own care, that is, disease self-management. The goal of this article is to present successful and unsuccessful interventions using patient self-management and to propose a model of integrated care more suitable to the needs of COPD patients. This is a narrative review and an opinion article. Many systematic reviews have shown positive outcomes for patients with COPD. These studies have in common a self-management intervention including an action plan in the event of an exacerbation embedded in an integrated health-care system coordinated by a case manager for educational sessions and regular communication. Recently published trials have brought controversy with respect to the effectiveness of self-management programmes, especially in patients with high burden of disease and co-morbidities. It may be more challenging to make the patient with high burden of disease a partner and not without risk of serious adverse events. Finally, our health-care delivery has to be well integrated and more coherent, that is, strategic alliance between primary and secondary care, and supported by interdisciplinary teams for patients with high-risk and complex COPD. Clinical practice has to be structured to address COPD throughout the disease spectrum, that is, secondary versus primary, team work, partnership, self-management and continuity of care.

PMID: 23382555 [PubMed - as supplied by publisher]

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Cigarette smoke-induced collagen destruction; key to chronic neutrophilic airway inflammation?

PLoS One. 2013;8(1):e55612

Authors: Overbeek SA, Braber S, Koelink PJ, Henricks PA, Mortaz E, Lotam Loi AT, Jackson PL, Garssen J, Wagenaar GT, Timens W, Koenderman L, Blalock JE, Kraneveld AD, Folkerts G

Abstract
BACKGROUND: Cigarette smoking induces inflammatory responses in all smokers and is the major risk factor for lung disease such as chronic obstructive pulmonary disease (COPD). In this progressive disease, chronic inflammation in the lung contributes to lung tissue destruction leading to the formation of chemotactic collagen fragments such as N-acetylated Proline-Glycine-Proline (N-ac-PGP). The generation of this tripeptide is mediated by a multistep pathway involving matrix metalloproteases (MMPs) 8 and 9 and prolyl endopeptidase (PE). Here we investigated whether cigarette smoke extract (CSE) stimulates human PMNs to breakdown whole matrix collagen leading to the generation of the chemotactic collagen fragment N-ac-PGP.
METHODOLOGY/PRINCIPAL FINDINGS: Incubating PMNs with CSE led to the release of chemo-attractant CXCL8 and proteases MMP8 and MMP9. PMNs constitutively expressed PE activity as well as PE protein. Incubating CSE-primed PMNs with collagen resulted in collagen breakdown and in N-ac-PGP generation. Incubation of PMNs with the tripeptide N-ac-PGP resulted in the release of CXCL8, MMP8 and MMP9. Moreover, we tested whether PMNs from COPD patients are different from PMNs from healthy donors. Here we show that the intracellular basal PE activity of PMNs from COPD patients increased 25-fold compared to PMNs from healthy donors. Immunohistological staining of human lung tissue for PE showed that besides neutrophils, macrophages and epithelial cells express PE.
CONCLUSIONS: This study indicates that neutrophils activated by cigarette smoke extract can breakdown collagen into N-ac-PGP and that this collagen fragment itself can activate neutrophils, which may lead in vivo to a self-propagating cycle of neutrophil infiltration, chronic inflammation and lung emphysema. MMP-, PE- or PGP-inhibitors can serve as an attractive therapeutic target and may open new avenues towards effective treatment of COPD.

PMID: 23383243 [PubMed - in process]

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Serum p53 antibody detection in patients with impaired lung function.

BMC Cancer. 2013 Feb 6;13(1):62

Authors: Mattioni M, Chinzari P, Soddu S, Strigari L, Cilenti V, Mastropasqua E

Abstract
ABSTRACT: BACKGROUND: TP53 gene mutations can lead to the expression of a dysfunctional protein that in turn may enable genetically unstable cells to survive and change into malignant cells. Mutant p53 accumulates early in cells and can precociously induce circulating anti-p53 antibodies (p53Abs); in fact, p53 overexpression has been observed in pre-neoplastic lesions, such as bronchial dysplasia, and p53Abs have been found in patients with Chronic Obstructive Pulmonary Disease, before the diagnosis of lung and other tobacco-related tumors. METHODS: A large prospective study was carried out, enrolling non-smokers, ex-smokers and smokers with or without the impairment of lung function, to analyze the incidence of serum p53Abs and the correlation with clinicopathologic features, in particular smoking habits and impairment of lung function, in order to investigate their possible role as early markers of the onset of lung cancer or other cancers. The p53Ab levels were evaluated by a specific ELISA in 675 subjects. RESULTS: Data showed that significant levels of serum p53Abs were present in 35 subjects (5.2%); no difference was observed in the presence of p53Abs with regard to age and gender, while p53Abs correlated with the number of cigarettes smoked per day and packs-year. Furthermore, serum p53Abs were associated with the worst lung function impairment. The median p53Ab level in positive subjects was 3.5 units/ml (range 1.2 to 65.3 units/ml). Only fifteen positive subjects participated in the follow-up, again resulting positive for serum p53Abs, and no evidence of cancer was found in these patients. CONCLUSION: The presence of serum p53Abs was found to be associated with smoking level and lung function impairment, both risk factors of cancer development. However, in our study we have not observed the occurrence of lung cancer or other cancers in the follow-up of positive subjects, therefore we cannot directly correlate the presence of serum p53Abs with cancer risk.

PMID: 23384026 [PubMed - as supplied by publisher]