CD11b immunophenotyping identifies inflammatory profiles in the mouse and human lungs.

The development of easily accessible tools for human immunophenotyping to classify patients into discrete disease endotypes is advancing personalized therapy. However, no systematic approach has been developed for the study of inflammatory lung diseases with often complex and highly heterogeneous disease etiologies. We have devised an internally standardized flow cytometry approach that can identify parallel inflammatory alveolar macrophage phenotypes in both the mouse and human lungs. In mice, lung innate immune cell alterations during endotoxin challenge, influenza virus infection, and in two genetic models of chronic obstructive lung disease could be segregated based on the presence or absence of CD11b alveolar macrophage upregulation and lung eosinophilia. Additionally, heightened alveolar macrophage CD11b expression was a novel feature of acute lung exacerbations in the SHIP-1(-/-) model of chronic obstructive lung disease, and anti-CD11b antibody administration selectively blocked inflammatory CD11b(pos) but not homeostatic CD11b(neg) alveolar macrophages in vivo. The identification of analogous profiles in respiratory disease patients highlights this approach as a translational avenue for lung disease endotyping and suggests that heterogeneous innate immune cell phenotypes are an underappreciated component of the human lung disease microenvironment.

Measuring performance to drive improvement: development of a clinical indicator set for general medicine.

BACKGROUND: There are delays in implementing evidence about effective therapy into clinical practice. Clinical indicators may support implementation of guideline recommendations. AIM: To develop and evaluate the short-term impact of a clinical indicator set for general medicine. METHODS: A set of clinical process indicators was developed using a structured process. The indicator set was implemented between January 2006 and December 2006, using strategies based on evidence about effectiveness and local contextual factors. Evaluation included a structured survey of general medical staff to assess awareness and attitudes towards the programme and qualitative assessment of barriers to implementation. Impact on documentation of adherence to clinical indicators was assessed by auditing a random sample of medical records before (2003-2005) and after (2006) implementation. RESULTS: Clinical indicators were developed for the following areas: venous thromboembolism, cognition, chronic heart failure, chronic obstructive pulmonary disease, diabetes, low trauma fracture, patient written care plans. The programme was well supported and incurred little burden to staff. Implementation occurred largely as planned; however, documentation of adherence to clinical indicators was variable. There was a generally positive trend over time, but for most indicators this was independent of the implementation process and may have been influenced by other system improvement activities. Failure to demonstrate a significant impact during the pilot phase is likely to have been influenced by administrative factors, especially lack of an integrative data documentation and collection process. CONCLUSION: Successful implementation in phase two is likely to depend upon an effective data collection system integrated into usual care.

Proliferation is not increased in airway myofibroblasts isolated from asthmatics.

Airway mesenchymal cells, such as myofibroblasts and airway smooth muscle cells, contribute to inflammation, airway remodelling and hyperresponsiveness in asthma by excessive proliferation and inflammatory mediator production. Using endobronchial biopsies obtained from both nonasthmatic and asthmatic subjects, in situ proliferation was assessed by immunostaining for cyclin D1. The number of immunoreactive cells increased with asthma severity and was restricted to the epithelium and subepithelial connective tissue. Despite increases in smooth muscle area, cyclin D1 was not detected in cells in intact muscle bundles. Biopsy-derived cell cultures were characterised as predominantly myofibroblasts, and were assessed to determine whether proliferation and cytokine production varied with asthma status. Cell enumeration showed that basal proliferation was similar in cells from nonasthmatics and asthmatics, and mitogenic responses to fibroblast growth factor-2, thrombin or serum were either reduced or unchanged in cells from asthmatics. Interleukin (IL)-1-dependent granulocyte-macrophage colony-stimulating factor and IL-8 release was increased in cell supernatants from asthmatics. Thus, increased rates of cellular proliferation identified in situ in the asthmatic airway occurred outside the expanded smooth muscle compartment. Although reduced proliferative responses were observed in cultured myofibroblasts from asthmatics, the increased cytokine production by these cells suggests that this contributes to and may perpetuate ongoing inflammation in asthma.

Hutchinson-Gilford progeria syndrome: clinical findings in three patients carrying the G608G mutation in LMNA and review of the literature.

BACKGROUND: Hutchinson-Gilford progeria syndrome (HGPS) is a rare premature ageing disorder that belongs to a group of conditions called laminopathies which affect nuclear lamins. Classical and atypical forms of HGPS have been reported and there are clinical overlaps with mandibulo-acral dysplasia and restrictive dermopathy. To date, mutations in two genes, LMNA and ZMPSTE24, have been found in patients with HGPS. The p.G608G LMNA mutation is the most commonly reported mutation. Correlations between genotype and phenotype in children with progeroid syndromes are beginning to emerge. OBJECTIVES: To establish whether the LMNA p.G608G mutation is associated with a particular phenotype of HGPS. METHODS: We reviewed the clinical features and skin histology of three children with HGPS associated with the p.G608G LMNA mutation, and compared our findings with those reported in the literature. RESULTS: Our patients shared a very similar presentation and clinical course. Skin changes were the earliest finding in all three. Skin histology showed nonspecific changes only. CONCLUSIONS: The LMNA p.G608G mutation results in a uniform phenotype through early to mid-childhood, in keeping with that described in classical HGPS. Skin changes are the earliest distinctive clinical finding and should prompt careful physical and radiological examination for other features of HGPS. Skin biopsy for histology is not a useful investigation when a diagnosis of HGPS is suspected.

An epidemiologic study of fatigue with relevance for the chronic fatigue syndrome.

We surveyed households in four rural Michigan communities to confirm a reported cluster of cases resembling chronic fatigue syndrome (CFS) and to study the epidemiology of fatigue in a rural area. Data were collected from 1698 households. We did not confirm the reported cluster. The prevalence of households containing at least one fatigued person was similar between communities thought to harbor the cluster and communities selected for comparison. Symptoms and features of generic forms of fatigue were very similar to those often attributed to CFS.

Modelling nutrition knowledge, attitudes, and diet-disease awareness: the case of dietary fibre.

Understanding how nutrition knowledge and attitudes vary across different population groups is critical for designing and evaluating nutrition education programmes and monitoring the nation's progress toward dietary goals. In this paper we use the Diet and Health Knowledge component of the USDA Continuing Survey of Food Intakes by Individuals to examine consumer knowledge of dietary fibre, fibre consumption attitudes and the awareness of fibre-related health problems. We use a latent variable probit model to estimate the relationships between an individuals's socio-demographic characteristics and his or her fibre knowledge, attitude and disease-awareness. The results suggest that the demographic profile of persons least knowledgeable about the fibre content of foods is low income, male, Black, Hispanic, smoker and low education levels. Add to this list younger individuals and one has a good description of those who lack information on the importance of eating plenty of grain products as well as those who lack awareness of fibre/disease links. The research suggests that messages about increasing fibre intake may have greatest success when targeted to individuals with some or all of these characteristics.

Private financing options for long-term care.

Private financing for long-term care now comes almost exclusively from out-of-pocket payments. Long-term-care costs quickly impoverish most elderly, resulting in Medicaid dependency. The consequences are profound for the western Sun Belt with its rapidly growing elderly population. Key private financing options are long-term-care individual retirement accounts (LTC/IRAs), home equity conversion, social-health maintenance organizations and long-term-care insurance. Study of data from the past half century suggests that the LTC/IRA approach would prove unsatisfactory for the purpose despite the intuitive appeal of this mechanism. Experience with home equity conversions is still very limited, and unresolved questions limit this approach to the role of a reserve option for now. While promising, social-health maintenance organizations are still in the experimental stages and not yet commercially available. Long-term-care insurance is currently sold on a thin market and emphasizes nursing home coverage. New approaches to private financing through long-term-care insurance seem to offer the best approach for immediate implementation.