Kinder and his colleagues assessed the prevalence of vitamin D deficiency in a cohort of patients with interstitial lung disease, who are often treated with corticosteroids. The detrimental effect of chronic use of corticosteroids on bone health has been well established, according to the researchers. Of the patients included in the study, 51 had interstitial lung disease and 67 had other forms of interstitial lung disease related to autoimmune connective tissue diseases.
A vitamin D insufficiency was defined as a serum level of less than 30 ng/mL. A level of less than 20 ng/mL was considered deficient. Both insufficient and deficient levels were prevalent in the study. In the overall sample, lower vitamin D levels were associated with reduced forced vital capacity (P=0.01). When the analysis was restricted to patients with connective tissue disease, both forced vital capacity and diffusing capacity of lung for carbon monoxide — a measure of the lung’s ability to transfer gases from the air to the blood — were significantly reduced (P<0.05 for both). After adjustment for several potential confounders — including age, corticosteroid use, race, and season, the presence of connective lung disease was a strong predictor of vitamin D insufficiency (OR 11.8, 95% CI 3.5 to 40.6).
According to the researchers, a pathogenic role of low vitamin D in the development of autoimmune diseases such as interstitial lung disease is plausible because of the immunoregulatory role of the biologically active form of vitamin D, 1,25-(OH)2D. “All cells of the adaptive immune system express vitamin D receptors and are sensitive to the action of 1,25-(OH)2D,” they wrote. “High levels of 1,25-(OH)2D are potent inhibitors of dendritic cell maturation with lower expression of major histocompatibility complex class II molecules, down-regulation of costimulatory molecules, and lower production of proinflammatory cytokines.” “A common theme in the immunomodulatory functions of vitamin D is that higher levels are immunosuppressive,” they continued, “which is consistent with a potential role for hypovitaminosis D in the pathogenesis of autoimmune disorders.”
In a statement, Len Horovitz, MD, a pulmonary specialist at Lenox Hill Hospital in New York City, commented that “vitamin D is known to promote wound healing, and to benefit the immune system. So it is not surprising to find that patients with immune lung disorders are vitamin D deficient.” He said that all of his patients are screened and treated for vitamin D deficiency with supplements. The study authors noted that further research is needed to determine whether supplementation is associated with improved outcomes. The study was limited, Kinder and his colleagues wrote, by its use of patients from a single center in Cincinnati.
In addition, the cross-sectional design of the study did not evaluate whether vitamin D supplementation is associated with any improved clinical outcomes. To examine that issue, the team called for prospective controlled interventional studies to determine whether vitamin D7 supplements can ameliorate symptoms and improve outcomes in connective tissue disease-related interstitial lung disease.
Source reference: Hagaman J, et al “Vitamin D deficiency and reduced lung function in connective tissue-associated interstitial lung diseases” Chest 2011; DOI: 10.1378/chest.10-0968.
In research described as “a stark warning” to those tempted to start smoking, scientists are reporting that cigarette smoke begins to cause genetic damage within minutes — not years — after inhalation into the lungs. Their report, the first human study to detail the way certain substances in tobacco cause DNA damage linked to cancer, appears in Chemical Research in Toxicology, one of 38 peer-reviewed scientific journals published by the American Chemical Society.
Stephen S. Hecht, Ph.D., and colleagues point out in the report that lung cancer claims a global toll of 3,000 lives each day, largely as a result of cigarette smoking. Smoking also is linked to at least 18 other types of cancer. Evidence indicates that harmful substances in tobacco smoke termed polycyclic aromatic hydrocarbons, or PAHs, are one of the culprits in causing lung cancer. Until now, however, scientists had not detailed the specific way in which the PAHs in cigarette smoke cause DNA damage in humans.
The scientists added a labeled PAH, phenanthrene, to cigarettes and tracked its fate in 12 volunteers who smoked the cigarettes. They found that phenanthrene quickly forms a toxic substance in the blood known to trash DNA, causing mutations that can cause cancer. The smokers developed maximum levels of the substance in a time frame that surprised even the researchers: Just 15-30 minutes after the volunteers finished smoking. Researchers said the effect is so fast that it’s equivalent to injecting the substance directly into the bloodstream.
“This study is unique,” writes Hecht, an internationally recognized expert on cancer-causing substances found in cigarette smoke and smokeless tobacco. “It is the first to investigate human metabolism of a PAH specifically delivered by inhalation in cigarette smoke, without interference by other sources of exposure such as air pollution or the diet. The results reported here should serve as a stark warning to those who are considering starting to smoke cigarettes,” the article notes. The authors acknowledged funding from the National Cancer Institute.
Cystic fibrosis is a genetic disease that causes a thick, sticky mucus to build up in the lungs and digestive tract. A clinical trial of a new drug called denufosol found that those given the medication for six months prevented some of the accumulation and improved performance on lung tests.
The Cystic Fibrosis Foundation estimates that about 30,000 children and adults in the United States have the condition that clogs the lungs and leads to life-threatening lung infections. The mucus also obstructs the pancreas and stops natural enzymes from helping the body break down and absorb food.
Cystic fibrosis is caused by a genetic mutation that disrupts the cystic fibrosis transmembrane regulator (CFTR) protein, an ion channel. Denufosol tetrasodium inhalation solution works by correcting ion transport in patients to enhance airway hydration and mucus clearance by increasing chloride secretion, inhibiting sodium absorption and increasing ciliary beat frequency.
Frank J. Accurso MD of the University of Colorado and colleagues included about 350 children with cystic fibrosis aged five and older in the study called TIGER-1, The Transport of Ions to Generate Epithelial Rehydration. All had a forced expiratory volume (FEV1) at least 75% of normal, indicating normal to mildly impaired lung function characteristic of early cystic fibrosis.
The patients were randomized to receive either 60 milligrams of inhaled denufosol three times daily or a matching placebo for 24 weeks. This was followed by another 24-week open-label safety extension phase.
The patients on the new medication had increase in FEV1 of 0.048 L, approximately 2% over baseline. In addition, the researchers found further lung improvement by 0.115L by the end of the open-label phase. The placebo group, when switched over to denofusol in the open-label phase, also improved by a mean 0.078 L in FEV1.
Big improvements weren't expected, says Accurso, because the drug is primarily designed to prevent or delay loss of lung function rather than act as a rescue therapy.
Denufosol appeared to be safe without serious adverse events or impaired growth of the young patients, suggesting it could be suitable as an early intervention. Intervention for cystic fibrosis early in its course has the potential to delay or prevent progressive changes that lead to irreversible airflow obstructions, the researchers say in their study published in the American Journal of Respiratory and Critical Care Medicine.
A second phase III trial, which is called TIGER-2, is ongoing which will incorporate a longer placebo-controlled treatment phase. Inspire Pharmaceuticals is targeting a potential US commercial launch of the drug for 2012, pending FDA approval.
Accurso FJ, et al “Denufosol Tetrasodium in Patients with Cystic Fibrosis and Normal to Mildly Impaired Lung Function” Am J Respir Crit Care Med 2011.
Steering clear of full-fat, fried, and processed foods is not just good for overall health, it could help prevent chronic lung conditions, a large UK study has revealed.
Led by Seif Shaheen, Professor of Respiratory Epidemiology at Barts and The London School of Medicine, the study – involving 1,551 men and 1,391 women with an average age of 66 – showed that those whose diet favoured fresh fruit and vegetables, oily fish and wholegrain products had far better lung function than those who chose a diet high in fat, sugar and processed food.
The diets of those involved were investigated to assess what kinds of food they consumed on a regular basis. Their lung function was also tested using a spirometer, a device which measures the amount of air that a person can blow out of their lungs in one second. This simple test illustrates how healthy the lungs are, and determines whether any blockage or obstruction exists in the airways. If the airways are obstructed, the person is diagnosed with Chronic Obstructive Pulmonary Disease (COPD).
The study also revealed that the beneficial effects of the sensible diet were particularly strong in men who smoked.
Lung health in particular may be positively affected by a sensible diet because of the antioxidants contained in fruit and wholegrains, and the omega-3 fatty acids found in oily fish – that protect the lungs against the adverse effects of smoking.
Professor Shaheen said: “Whilst cessation of smoking is still the number one way to improve lung health, this study is important because it suggests that cases of COPD might be prevented if people, especially male smokers, ate more fruit and vegetables, oily fish and wholegrain cereals, and less white bread, sugar, full fat dairy products, fried food and processed meat. However, the only way to confirm this would be to carry out a randomised controlled trial.”
The factors instrumental in triggering latent tuberculosis (TB) infection to progress into active disease have long remained elusive to researchers. New insight into the mystery is provided by Professor David Russell, speaking at the Society for General Microbiology's spring meeting in Edinburgh today. His work could help develop innovative strategies for treating the disease.
Professor Russell and his group at Cornell University in New York, USA, have demonstrated that TB-causing bacteria are able to hijack fat metabolism in the host to drive the progression of the disease. The team's research shows that Mycobacterium tuberculosis (Mtb) is able to stimulate macrophages – the immune cells the bacterium infects – to accumulate fat droplets, turning them into “foamy” cells. This cellular transformation can trigger a reawakening of the TB infection from its latent state.
Following initial infection by Mtb, the infected immune cells in the body can clump together in the lungs in a cellular mass that is surrounded by a fibrous cuff. This containing structure, called a
tubercle, physically protects the bacteria from being destroyed by the immune system. This allows them to persist inside the host for years during a latent period in which the host shows no symptoms. The respiratory infection is reactivated only in a small percentage of individuals (often those who are immunosuppressed) in whom it progressively destroys lung tissue. Very little is known about the exact causes of reactivation and the relative roles of the host and the pathogen.
Professor Russell's group discovered that inside the tubercle, surface molecules of Mtb prompted host macrophage cells to take up vast quantities of cholesterol-type lipids from the surrounding blood
vessels. “We think that the lipids in the newly-formed foamy cell are then expelled into the cellular environment, which contributes to the collapse of the tubercle,” he said.
Once freed from their containing structure, the infectious bacteria are able to leak out into the airways where they can progressively destroy lung tissue. “If our model is correct, it has huge implications for
vaccines and chemotherapy programmes. A more detailed knowledge of the bacterium's life cycle and its host interactions will allow us to spot new targets for drugs – opening up new possibilities for treatment,” said Professor Russell.
Apples could become the next fish when it comes to boosting health.
In March 2005 Cornell University scientists discovered that phytochemicals in apples could help prevent breast cancer, found in a mouse study. Study author Rui Hai Lui concluded eating apples “may be an effective strategy for cancer protection” Studies also suggest that apples can thwart lung, prostate, pancreatic and other digestive cancers.
Quercitin found in apples might even prevent lung damage in smokers, found by UCLA researchers and published May 2008. Dr. Zuo-Feng Zhang, a researcher at UCLA's Jonsson Cancer Center and a professor of public health and epidemiology. “The findings were especially interesting because tobacco smoking is the major risk factor for lung cancer. The naturally occurring chemicals may be working to reduce the damage caused by smoking.”
The health benefits of apples also extend to the brain. A study underwritten by the apple industry found that mice with Alzheimer's disease and even normal mice experienced memory improvement from receiving apple juice concentrate in their water. Two to 3 glasses of apple juice a day should be enough and it's important to combine apples with an otherwise balanced diet.
Professor Thomas Shea who conducted the study starting in 2002 says mice that drank too much apple juice “became bloated and lethargic”, negating the positive effects of apple juice for boosting memory.
Pectin in apples and other fruit may play a key role in lowering bad cholesterol, shown in several observational studies. Apples are also high in soluble fiber. The American Heart Association recommends soluble and insoluble fiber intake daily as part of a heart healthy diet. Apple pulp is a soluble and apple skin is an insoluble fiber. The Apple Association also published a study May 2008 suggesting that apple juice antioxidants might prevent atherosclerosis, found in a rodent study and published in Molecular Nutrition & Food Research. Additional benefits include reducing the chances of metabolic syndrome that leads to diabetes and heart disease, reported by the U.S. Apple Association.
This year, University of Illinois at Urbana-Champaign published findings that soluble fiber increased production of the anti-inflammatory protein called interleukin-4. The amount of soluble fiber needed to keep infection at bay – for instance from eating apples – is obtainable and not pharmaceutical. For the study researchers used citrus based pectin.
According to Gregory Freund, a professor in the University of Illinois' College of Medicine and a faculty member in the College of Agriculture, Consumer and Environmental Sciences' Division of Nutritional Sciences, “It's possible that supplementing a high-fat diet with soluble fiber could reduce the negative effects of a high fat diet, “even delaying the onset of diabetes.” Apples are an excellent source of soluble and insoluble fiber, making them an especially appealing addition to the diet.
Apples are not a panacea that can fight disease, but they do have a wide array of health benefit. It's important to eat a variety of fruits and vegetables throughout the day. Added to a balanced, nutritious and heart healthy diet, apples might rival fish for their health benefits.
Dr. Nick and his colleagues analyzed epidemiological and health data on 156 CF patients over 40 year of age who receive care at National Jewish Health, the largest adult cystic fibrosis clinic in the nation. In addition, data were analyzed on nearly 3,000 patients from around the nation who were included in the Cystic Fibrosis Foundation Patient Registry from 1992-2007.
The researchers found that the fate of females changes considerably in the older CF population. It has long been recognized that a “gender gap” is present in CF, favoring males. Historically, females have been diagnosed later, had a poorer prognosis, and survived fewer years than males.
Accordingly, Dr. Nick's analysis showed that fewer females diagnosed as children survived to age 40. However, among those diagnosed as adults, females represented a significant majority, accounting for 72 percent of patients in Colorado and 54 percent nationally. Among the adult diagnosed patients, females survived on average 9 to 14 years longer than males.
The complex factors that account for the differential fate of female CF patients is not understood, although Dr. Nick believes it could be a mixture of behavioral and biological factors.
Dr. Nick's findings also indicate that patients diagnosed as adults do not really have milder diseases — as is commonly believed — just a delayed onset of an equally severe form of the disease. Although patients diagnosed as adults live longer than those diagnosed as children, the adult-diagnosed patients lose lung function as rapidly those diagnosed in childhood, and approximately 85% die of respiratory failure or post-transplant complications.
Dr. Nick believes there is a significant number of adults whose CF remains undiagnosed. His analysis indicates that once those patients are accurately diagnosed, proper care can significantly improve their health. Patients diagnosed as adults and subsequently followed at a CF center reversed progressive lung function decline and improved their lung function for at least four years. Older patients commonly do not get specialized CF care. It is generally recognized that the team approach to treatment provided by the 112 CF Foundation-accredited Care Centers results in better clinical outcomes. However, less than half of long-term CF survivors continued to be seen at CF Centers as they pass 40 years, with the fewest among the adult-diagnosed patients.
“In the coming years, more and more cystic fibrosis patients will be living into their 40s, 50s and beyond,” said Dr. Nick. “Our findings concerning the role of gender, in survival, progression of disease, and type of care in current long-term survivors provides important insights that will help us prepare for better treatment of the steadily aging CF population.”
Avoid eating meals high in fat, especially if you suffer from asthma, urges Australian researchers after finding the fat leads to inflamed breathing passages and hinders drug interventions.
Lisa Wood, PhD, research fellow and lecturer in the biomedical sciences and pharmacy department of Hunter Medical Research Institute, at the University of Newcastle, led the study with a team of researchers and presented their findings at ATS 2010, the international meeting of the American Thoracic Society, in New Orleans.
The researchers challenged 14 non-obese asthmatics and 16 obese participants to a high-fat diet (1,000 calories with 52%/60g of fat) of burgers and fried potatoes and another group of 16 non-obese asthmatics to eat a low-fat yogurt diet (200 calories, 13%/3g fat). “Induced sputum samples were collected at baseline and at 4 hours” according to the study's abstract.
“Subjects who had consumed the high-fat meal had an increase in airway neutrophils and TLR4 mRNA gene expression from sputum cells, that didn't occur following the low fat meal, ” said Wood.
She continued, “The high fat meal impaired the asthmatic response to albuterol. In subjects who had consumed a high fat meal, the post-albuterol improvement in lung function at three and four hours was suppressed.”
The researchers were surprised to find that the fatty diet also impacted the effectiveness of asthma medications, like albuterol. Wood added, “This is the first study to show that a high fat meal increases airway inflammation, so this is a very important finding. The observation that a high fat meal changes the asthmatic response to albuterol was unexpected as we hadn't considered the possibility that this would occur.”
It's unclear how and why fat not only inflames the airways but also prevents known asthma therapies from working. The researchers intend to design “more studies to investigate this effect. We are also investigating whether drugs that modify fat metabolism could suppress the negative effects of a high fat meal in the airways. If these results can be confirmed by further research, this suggests that strategies aimed at reducing dietary fat intake may be useful in managing asthma.”
Whether you have asthma or not is becoming increasingly more important for heart and now lung health to avoid the fat.
Ms. Agler and colleagues reviewed data compiled by the Women's Health Study, a multi-year, long-term effort ending in 2004 that focused on the effects of aspirin and vitamin E in the prevention of cardiovascular disease and cancer in nearly 40,000 women aged 45 years and older. Study participants were randomized to receive either 600 mg of vitamin E or a placebo every other day during the course of the research.
Although fewer women taking vitamin E developed COPD, Ms. Agler noted the supplements appeared to have no effect on asthma, and women taking vitamin E supplements were diagnosed with asthma at about the same rate as women taking placebo pills. Importantly, Ms. Agler noted the decreased risk of COPD in women who were given vitamin E was the same for smokers as for non-smokers.
Ms. Agler said further research will explore the way vitamin E affects the lung tissue and function, and will assess the effects of vitamin E supplements on lung diseases in men. “If results of this study are borne out by further research, clinicians may recommend that women take vitamin E supplements to prevent COPD,” Ms. Agler noted. “Remember that vitamin E supplements are known to have detrimental effects in some people; for example vitamin E supplementation increased risk of congestive heart failure in cardiovascular disease patients. Broader recommendations would need to balance both benefits and risks. “
Led by Dr Roger Hurst, the New Zealand-based researchers examined the effects of the anthocyanidin-rich blackcurrant extract on cells from lung tissue. The researchers focussed on a compound called eotaxin-3 or CCL26, which is expressed in the lungs after stimulation of the cells by cytokine interleukin-4 (IL-4). According to their findings, epigallocatechin (EGC) worked in conjunction with other natural immune responses to suppress CCl26 expression, and therefore inflammation. Furthermore, these actions were distinct from the inflammation-reducing activity of anthocycanins, said the researchers.
“The bioavailability of plant-derived phytochemicals, although not the focus of this particular study, is an important consideration in the design of a functional food,” wrote Dr Hurst and his co-workers. “In particular, blackcurrant- derived proanthocyanidins mainly (480 per cent) consist of high molecular weight polymers, however, recent findings show that these large proanthocyanidins can be broken down by chemical, enzymatic and/or resident microflora in various regions of the digestive tract to release small oligomers and monomers that are easily absorbed, such as EGC and epicatechin. “Therefore, it is feasible that blackcurrant metabolites, such as EGC, may be able to modulate eotaxin expression in lung tissue,” they added.
Plant & Food Research's Dr Roger Hellens, Genomics Science Group Leader, will be presenting at the upcoming NutraIngredients Antioxidants 2010 Conference in Brussels on the subject of super Vegetables.
Source: Molecular Nutrition and Food Research
“Blackcurrant proanthocyanidins augment IFN-gamma-induced suppression of IL-4 stimulated CCL26 secretion in alveolar epithelial cells”
Authors: S.M. Hurst, T.K. McGhie, J.M. Cooney, D.J. Jensen, E.M. Gould, K.A. Lyall, R.D. Hurst