Inhalation Delivery of Protein Therapeutics.

Inflamm Allergy Drug Targets. 2013 Mar 19;

Authors: Kane C, Oneil K, Conk M, Picha K

Abstract
Inhaled therapeutics are used routinely to treat a variety of pulmonary diseases including asthma, COPD and cystic fibrosis. In addition, biologic therapies represent the fastest growing segment of approved pharmaceuticals. However, despite the increased availability of biologic therapies, nearly all inhaled therapeutics are small molecule drugs with only a single inhaled protein therapeutic approved. There remains a significant unmet need for therapeutics in pulmonary diseases and biologic therapies with potential to alter disease progression represent a significant opportunity to treat these challenging diseases. This review provides a background into efforts to develop inhaled biologic therapies and highlights some of the associated challenges. In addition, we speculate on the ideal properties of a biologic therapy for inhaled delivery.

PMID: 23517644 [PubMed - as supplied by publisher]

Engineering approaches to develop the next generation of antibodies to respiratory targets.

Inflamm Allergy Drug Targets. 2013 Mar 19;

Authors: Vousden KA, Clarke DL, Lowe DC

Abstract
Chronic respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD) represent a significant health burden worldwide and are a major unmet medical need. Asthma affects over 300 million people and leads to 250,000 deaths per year, with an increasing prevalence particularly in developing countries. Although a large proportion of asthmatics are maintained on beta agonists and corticosteroids, there still remains a group of patients where these medicines fail to modulate symptoms and who may therefore benefit from monoclonal antibody based drugs that are aimed at controlling the disease. COPD is a cigarette smoke-driven chronic inflammatory airway disease with an increasing global prevalence. Given that current therapies fail to prevent disease progression or mortality, this patient population is also a focus for the development of monoclonal antibody therapies. At present anti-IgE (omalizumab, Xolair ®) is the only monoclonal antibody based drug approved in the respiratory space for the treatment of asthma. However, an increasing number of antibodies targeting key mediators/pathways of disease are in clinical development for both asthma and COPD, including targeting the Th2 pathway for asthma (anti-IL-4/5/13) and the pro-inflammatory cytokine IL-1 for COPD. This review will examine the antibody engineering approaches used to develop the next generation of antibodies, with a focus on respiratory disease.

PMID: 23517646 [PubMed - as supplied by publisher]

Association between Respiratory Syncytial Virus Hospitalizations in Infants and Respiratory Sequelae: Systematic Review and Meta-Analysis.

Pediatr Infect Dis J. 2013 Mar 20;

Authors: Régnier S, Huels J

Abstract
BACKGROUND:: The association between hospitalization for respiratory syncytial virus (RSV) infection in infancy and asthma/wheezing in later life has long been studied. However, no published studies have combined systematic review and meta-analysis of existing evidence. PURPOSE:: To quantify the link between RSV hospitalization in early life and subsequent diagnosis of asthma. METHOD:: A systematic search was conducted using MEDLINE and EMBASE databases. Studies were selected for meta-analysis if they assessed the association between RSV-confirmed hospitalization for up to 3 years of age and asthma/wheezing later in life. Potential sources of heterogeneity were identified by stratified analysis. RESULTS:: Twenty articles representing 15 unique studies of 82008 unique individuals (including 1533 with RSV-confirmed hospitalization) were selected for meta-analysis. Children who had RSV disease in early life had a higher incidence of asthma/wheezing in later life (odds ratio: 3.84; 95% confidence interval: 3.23-4.58). There was moderate heterogeneity between studies (I=45%). The association was found to decrease with age at follow-up, consistent with the findings of longitudinal studies. When age at follow-up was considered, heterogeneity was low (residual I=17%). LIMITATIONS:: Study quality was generally poor because randomization to hospitalization for RSV infection was not possible, appropriate blinding was rare, and adjustment for confounding variables was not always appropriate. CONCLUSIONS:: The meta-analysis suggests an association between infant RSV hospitalization and respiratory morbidity that decreases with age. If the association is causal, the development of an effective vaccine against RSV could decrease the burden of asthma.

PMID: 23518824 [PubMed - as supplied by publisher]

Trends in the use of antiasthmatic medications in Morocco (1999-2010).

Springerplus. 2013 Dec;2(1):82

Authors: Ghanname I, Ahid S, Berrada G, Belaiche A, Hassar M, Cherrah Y

Abstract
BACKGROUND: Asthma is a big public health problem in Morocco. The drug therapy existing in Morocco is currently insufficient because of the low purchasing power and the low health insurance coverage available to the average citizen in Morocco. In this study we evaluated the consumption of antiasthmatics in Morocco during the period 1999-2010, the classes of used drugs and the generics' market share.
METHODS: We used sales data from the Moroccan subsidiaries of the IMS Health "Intercontinental Marketing Service". The consumption volume was converted to Defined Daily Doses (DDDs).
RESULTS: During 1999-2010, antiasthmatics's consumption increased from 3.91 to 14.47 DDD per 1000 inhabitants per day. In 2010, the association Beta-2-mimetic-Glucocorticosteroids were the most consumed (8.53 DDD/1000 Inhabitants/day) followed by the short-acting inhaled Beta-2-mimetic (4 DDD/1000 Inhabitants/day) and inhaled Glucocorticosteroids alone accounted for 1.13 DDD/1000 Inhabitants/day. The largest consumption share in volume was held by the short-acting inhaled Beta-2-mimetic (42%) followed by the combination Beta-2-mimetic-Glucocorticosteroids (38%). Between 1999 and 2010, the market for generic antiasthmatics increased from 1.84 to 2.18 DDD/1000 Inhabitants/day. The ratio of the monthly average cost of treatment to the minimum wage in Morocco decreased from 10.8% in 1999 to 7.11% in 2010.
CONCLUSION: Antiasthmatics' consumption in Morocco has undergone significant changes between 1999 and 2010. However, the availability of these drugs expressed as the Average Monthly Expenditure/Guaranteed Minimum Wage ratio improved. Despite this, the use of antiasmathics in Morocco remains low.

PMID: 23519830 [PubMed - as supplied by publisher]