Personalised Medicine and Asthma Diagnostics/Management.

Curr Allergy Asthma Rep. 2012 Dec 5;

Authors: Wadsworth SJ, Sandford AJ

Abstract
Human beings come in all shapes and sizes. Heterogeneity makes life interesting, but leads to inter-individual variation in disease susceptibility and response to therapy. One major health challenge is to develop "personalised medicine"; therapeutic interventions tailored to an individual to ensure optimal treatment of disease. Asthma is a heterogeneous disease with several different phenotypes triggered by multiple gene-environment interactions. Inhaled corticosteroids and β2-agonists have been the mainstay asthma therapies for 30 years, but they are not effective in all patients, while high costs and side-effects also drive the need for better targeted treatment of asthma. Pharmacogenetics is the study of variations in the genetic code for proteins in signaling pathways targeted by pharmacological therapies. Biomarkers are biological markers obtained from patients that can aid in asthma diagnosis, prediction of treatment response, and monitoring of disease control. This review presents a broad discussion of the use of genetic profiling and biomarkers to better diagnose, monitor, and tailor the treatment of asthmatics. We also discuss possible future developments in personalised medicine, including the construction of artificially engineered airway tissues containing a patient's own cells for use as personalised drug-testing tools.

PMID: 23212666 [PubMed - as supplied by publisher]

Human coronaviruses: insights into environmental resistance and its influence on the development of new antiseptic strategies.

Viruses. 2012;4(11):3044-68

Authors: Geller C, Varbanov M, Duval RE

Abstract
The Coronaviridae family, an enveloped RNA virus family, and, more particularly, human coronaviruses (HCoV), were historically known to be responsible for a large portion of common colds and other upper respiratory tract infections. HCoV are now known to be involved in more serious respiratory diseases, i.e. bronchitis, bronchiolitis or pneumonia, especially in young children and neonates, elderly people and immunosuppressed patients. They have also been involved in nosocomial viral infections. In 2002-2003, the outbreak of severe acute respiratory syndrome (SARS), due to a newly discovered coronavirus, the SARS-associated coronavirus (SARS-CoV); led to a new awareness of the medical importance of the Coronaviridae family. This pathogen, responsible for an emerging disease in humans, with high risk of fatal outcome; underline the pressing need for new approaches to the management of the infection, and primarily to its prevention. Another interesting feature of coronaviruses is their potential environmental resistance, despite the accepted fragility of enveloped viruses. Indeed, several studies have described the ability of HCoVs (i.e. HCoV 229E, HCoV OC43 (also known as betacoronavirus 1), NL63, HKU1 or SARS-CoV) to survive in different environmental conditions (e.g. temperature and humidity), on different supports found in hospital settings such as aluminum, sterile sponges or latex surgical gloves or in biological fluids. Finally, taking into account the persisting lack of specific antiviral treatments (there is, in fact, no specific treatment available to fight coronaviruses infections), the Coronaviridae specificities (i.e. pathogenicity, potential environmental resistance) make them a challenging model for the development of efficient means of prevention, as an adapted antisepsis-disinfection, to prevent the environmental spread of such infective agents. This review will summarize current knowledge on the capacity of human coronaviruses to survive in the environment and the efficacy of well-known antiseptic-disinfectants against them, with particular focus on the development of new methodologies to evaluate the activity of new antiseptic-disinfectants on viruses.

PMID: 23202515 [PubMed - in process]

Related Articles

Human papillomavirus and diseases of the upper airway: head and neck cancer and respiratory papillomatosis.

Vaccine. 2012 Nov 20;30 Suppl 5:F34-54

Authors: Gillison ML, Alemany L, Snijders PJ, Chaturvedi A, Steinberg BM, Schwartz S, Castellsagué X

Abstract
Human papillomavirus (HPV) infection is causally associated with benign and malignant diseases of the upper airway, including respiratory papillomatosis and oropharyngeal cancer. Low-risk HPV types 6 and 11 are the predominant cause of papillomatosis, whereas only HPV16 definitively satisfies both molecular and epidemiological causal criteria as a carcinogenic or high-risk type in the upper airway. HPV16 E6/E7 mRNA expression and integration are observed predominantly among oropharyngeal cancers, and experimental models have shown E6/E7 expression to be necessary for the initiation and maintenance of the malignant phenotype of these cancers. From an epidemiological perspective, a strong and consistent association between markers of HPV16 exposure and oropharyngeal cancer has been demonstrated in numerous case-control studies. HPV-positive oropharyngeal cancers have also been shown to be distinct from HPV-negative head and neck squamous cell cancers with regard to risk-factor profiles, molecular genetic alterations, population-level incidence trends over time, and prognosis. Tumor HPV status (as determined by certain HPV16 in situ hybridization assays or certain p16 immunohistochemistry assays) is the strongest determinant of survival for patients with local-regionally advanced oropharyngeal cancer: patients with HPV-positive cancer have at least a 50% improvement in overall survival at 5 years, which is equivalent to an approximate 30% difference in absolute survival. Thus, HPV status determination is now part of the routine diagnostic evaluation for prognostication. Preliminary evidence indicates that a small proportion of head and neck cancers may be caused by additional HPV types (e.g., 18, 31, 33, 35) and that HPV-caused cancers may rarely arise from non-oropharyngeal sites (e.g., the oral cavity, nasopharynx, and larynx). Whether or not HPV vaccination has the potential to prevent oral HPV infections that lead to cancer or papillomatosis in the upper airway is currently unknown, as is the potential for secondary prevention with HPV detection. This article forms part of a special supplement entitled "Comprehensive Control of HPV Infections and Related Diseases" Vaccine Volume 30, Supplement 5, 2012.

PMID: 23199965 [PubMed - in process]

Related Articles

Palliative care in COPD patients: is it only an end-of-life issue?

Eur Respir Rev. 2012 Dec 1;21(126):347-54

Authors: Carlucci A, Guerrieri A, Nava S

Abstract
The presence of acute or chronic respiratory failure is often seen as a terminal phase of chronic obstructive pulmonary disease. A great variability in end-of-life practice is observed in these patients mainly because physicians are not always able to correctly predict survival. There is a need for a clear discussion about decision making earlier than when acute respiratory failure ensues. Indeed, a perceived poor quality of life does not necessarily correlate with a clear willingness to refuse invasive or noninvasive mechanical ventilation. It has been suggested to start palliative care earlier, together with curative and restorative care, when there is an increased intensity of symptoms. The patients eligible for palliative care are those complaining of breathlessness, pain, fatigue and depression, which in some studies accounted for a prevalence much higher than 50%. Among comfort measures for palliation, oxygen is frequently prescribed even when the criteria for long-term home oxygen therapy are not met; however, when compared with air, no benefits on dyspnoea have been found. The only drug with a proven effect on dyspnoea is morphine, but not when it is delivered with a nebuliser. Finally, noninvasive ventilation may be used only as a comfort measure for palliation to maximise comfort by minimising adverse effects.

PMID: 23204123 [PubMed - in process]