Vitamin D deficiency and chronic lung disease.

Vitamin D deficiency is increasingly being recognized as a prevalent problem in the general population. Patients with chronic lung diseases such as asthma, cystic fibrosis, chronic obstructive lung disease and interstitial pneumonia appear to be at increased risk for vitamin D deficiency for reasons that are not clear. Several studies indicate that vitamin D possesses a range of anti-inflammatory properties and may be involved in processes other than the previously believed functions of calcium and phosphate homeostasis. Various cytokines, cellular elements, oxidative stress and protease/antiprotease levels appear to affect lung fibroproliferation, remodelling and function, which may be influenced by vitamin D levels. Chronic lung diseases such as asthma and chronic obstructive lung disease have also been linked to vitamin D on a genetic basis. This immune and genetic influence of vitamin D may influence the pathogenesis of chronic lung diseases. A recent observational study notes a significant association between vitamin D deficiency and decreased pulmonary function tests in a large ambulatory population. The present review will examine the current literature regarding vitamin D deficiency, its prevalence in patients with chronic lung disease, vitamin D anti-inflammatory properties and the role of vitamin D in pulmonary function.

Advanced lung disease: quality of life and role of palliative care.

Advanced restrictive lung diseases remain a challenge for both the clinician and patient alike. Because there are few available treatment options that prolong survival for patients with diseases such as idiopathic pulmonary fibrosis, improvement in quality of life and palliation of significant symptoms become realistic treatment goals. Several validated instruments that assess quality of life and health-related quality of life have demonstrated the dramatic impact that lung disease has on patients. Quality-of-life assessments of patients with interstitial lung disease have commonly cited respiratory complaints as problematic, but other distressing symptoms often not addressed include fear, social isolation, anxiety, and depression. Not only do respiratory symptoms limit this patient population, but the awareness of decreased independence and ability for social participation also has an impact on the quality of life. Some patients describe a deepened spiritual well-being during their disease process; however, many patients' mental health suffers with experiences of fear, worry, anxiety, and panic. Many patients express desire for more attention to end-of-life issues from their physicians. Fears of worsening symptoms and suffocation exist with an expressed desire by most to die peacefully with symptom control. Interventions to improve quality of life are largely directed at symptom control. Pharmacologic and nonpharmacologic interventions have been helpful in relieving dyspnea. Studies have demonstrated that the use of supplemental oxygen in the face of advancing hypoxemia can have both positive and negative effects on quality of life. Patients using nasal prongs describe feelings of self-consciousness, embarrassment, and social withdrawal. Pulmonary rehabilitation is recommended, with some studies noting increased quality-of-life scores and decreased sensations of dyspnea. Sleep deprivation and poor sleep quality also have a negative impact on quality of life. Recognition and correction of nocturnal hypoxemia and other sleep disturbances should enhance quality of life in patients with restrictive lung disease; however, there is currently no evidence to support this claim. End-of-life care needs more attention by clinicians in the decision-making and preparatory phase. Physicians need to maintain their focus on quality-of-life issues as medical management shifts from curative therapies to comfort management therapies. Palliative care and hospice appear to be underused in patients with advanced diseases other than cancer. Because the only curative option for some end-stage restrictive lung diseases is lung transplantation, if transplantation is not an option, palliation of symptoms and hospice care may offer patients and families the opportunity to die with dignity and comfort.

An optimized whole blood method for flow cytometric measurement of ZAP-70 protein expression in chronic lymphocytic leukemia.

BACKGROUND: ZAP-70 protein expression has been proposed as a marker for immunoglobulin heavy chain mutational status, which some studies have correlated with disease course in B-cell chronic lymphocytic leukemia (CLL). Studies published to date measuring levels of expression of ZAP-70 intracellular protein using flow cytometry have demonstrated poor performance, as defined by the difference in signal in known positive and negative lymphocyte populations. METHODS: A recently published method (Chow S, Hedley DW, Grom P, Magari R, Jacobberger JW, Shankey TV, Cytometry A 2005;67:4-17) to measure intracellular phospho-epitopes was optimized using a design of experiments (DOE) approach to provide the best separation of ZAP-70 expression in positive T- or NK-cells as compared to negative B-cells in peripheral blood samples. A number of commercially available anti-ZAP-70 antibody-conjugates were screened using this methodology, and the antibody-conjugate showing the best performance was chosen to develop a four-color, five antibody assays to measure ZAP-70 levels in whole blood specimens. RESULTS: Using the optimized fixation and permeabilization method, improvement in assay performance (signal-to-noise, S/N) was seen in most of the antibodies tested. The custom SBZAP conjugate gave the best S/N when used in conjunction with this optimized fixation /permeabilization method. In conjunction with carefully standardized instrument set-up protocols, we obtained both intra- and interlaboratory reproducibility in the analysis of ZAP-70 expression in whole blood samples from normal and CLL patients. CONCLUSIONS: The development of a sensitive, specific and highly reproducible ZAP-70 assay represents only the first essential step for any clinical assay. The universal implementation of a validated data analysis method and the establishment of methodology-based cutoff points for clinical outcomes must next be established before ZAP-70 protein analysis can be routinely implemented in the clinical laboratory.

Predicting survival of lung transplantation candidates with idiopathic interstitial pneumonia: does PaO(2) predict survival?

OBJECTIVE: To find a parameter that would discriminate between the patients with idiopathic interstitial pneumonia who survived to undergo transplantation and those who died while waiting to undergo transplantation. METHODS: A retrospective review was performed of all lung transplant referrals for idiopathic interstitial pneumonia that were listed with United Network for Organ Sharing at the University of California San Diego from January 1990 to February 1999. Of the 331 patients who were listed, 48 met the eligibility criteria. Patient demographics, radiographic studies, pathology reports, and the results of resting and exercise cardiopulmonary function tests were recorded from each patient's chart. Patients were divided into the following two groups: those patients who survived until transplantation and those still waiting were classified as "alive"; and those patients who died before undergoing transplantation were classified as "deceased." RESULTS: Forty-three of 48 patients had a pathologic diagnosis. The cohort included 25 patients with usual interstitial pneumonitis, 3 patients with nonspecific interstitial pneumonitis, 1 patient with desquamative interstitial pneumonitis, and 14 patients with interstitial lung disease of unknown etiology. The only significant difference between the two groups was resting PaO(2) (p = 0.035). A stepwise multivariate analysis demonstrated that PaO(2) and FEV(1)/FVC ratio were significantly associated with survival (hazards ratio, 1.06; confidence interval, 0.99 to 1.13; p = 0.019). CONCLUSIONS: A survival analysis using PaO(2) and FEV(1)/FVC ratio values proved to be statistically significant, but a prospective trial is needed to determine the clinical relevance of these parameters for predicting survival in patients with idiopathic interstitial pneumonia.