Tax Tips for CFer's

Here are the CF Foundation's Tax Tips for CFer's:

TAX TIPS FOR FOOD EXPENSE DEDUCTIONS

Some people with CF and their families may have trouble paying for the cost of food needed to meet the high nutritional requirements of CF. Federal tax law allows people to deduct a portion of the total food expenses that exceeds the amount a healthy person spends on food. This expense should be added to other expenses for medical care, and can be deducted if the total expense is greater than 7 ½ percent of the individual's gross income.

SUMMARY

Buying food for people with CF can be very expensive. Depending on the impact of CF on the digestive system, a person with CF may consume two, three or more times the amount of food that a person without CF would eat. Also, individuals with CF are required to eat special foods, which can represent a large expense. If you or your family face this problem, you may be able to deduct part of your total food expenses as a medical expense on your federal income tax return.

HERE’S HOW...

Federal tax law classifies certain special food purchased for an illness as a medical expense. However, only a portion of one’s total expenses for food may be deductible. That is, only the portion of expenses that exceeds the amount a healthy person spends on food is deductible. The Internal Revenue Service (IRS) applies this rule in a very strict manner and will challenge taxpayers on issues involving documentation of actual expenses, whether the expenses are medically necessary, and whether any part of such expenses exceeds nutritional needs. If you decide to use this tax benefit, please refer to the guidelines below.

HERE’S WHAT TO DO...

Consult with the nutritionist and/or physician at your CF care center.
If a specific diet has been prescribed for you or a family member, request that the care center nutritionist or physician provide you with written confirmation designating the following:

• Amount of food needed
• Type of food needed (including caloric or food supplements such as MCT oil, Portagen, Ensure or special formulas)
• Why the food is needed
• Consequences of not following the diet
  

Establish a system for recording the cost of food used by the CF patient.
It is very important that you keep accurate records of the amount, type, and cost of food eaten by the person with CF to support a claim. People have claimed this deduction based on accurate records, including store receipts kept over a two-week period, and then used that as an average on which to determine annual totals.

Keep a record of total food eaten for at least 14 days.

Make a special note when you buy higher-cost foods required by the diet.

Since these are tax records, keep them as long as you keep your other financial records.
Your records should also include information on the nutritional needs of healthy individuals of the same age and sex as the CF patient.

We have provided a list of the cost of nutritional needs for healthy individuals that is prepared monthly by the U.S. Department of Agriculture.

http://www.cnpp.usda.gov/Publications/FoodPlans/2009/CostofFoodJan09.pdf

This USDA chart assumes that food for all meals and snacks is purchased at the store and prepared at home. In addition, the costs given are for individuals in a family with 4 people. The following changes are suggested for other family sizes.

1 person family, add 20 percent
2 persons, add 10 percent
3 persons, add 5 percent
5 or 6 persons, subtract 5 percent
7 or more persons, subtract 10 percent

This information is important for providing a way to compare the kind and amount of food purchased for, and consumed by, a person with CF. If you require more information, please contact your CF care center or the CF Foundation's National Office for assistance.
Only claim as a medical deduction the amount of food that exceeds the costs for a person without CF.

Be sure that the costs claimed are only for the food included in the diet that has been prescribed. For example, if a person without CF eats two eggs for breakfast, and your records show a six-egg omelet, you would be able to deduct the cost of four eggs, not all six eggs.

HERE’S WHAT THE LAW SAYS...

If you decide to claim a tax deduction for food purchased to treat a person with CF in your family, you should know about the law regarding this particular tax benefit. Section 213(a) of the Internal Revenue Code of 1986, as amended, states in relevant part:

"213(a) Allowance of Deduction. - There shall be allowed as a deduction the expenses paid during the taxable year, not compensated for by insurance or otherwise, for medical care of the taxpayer, his spouse, or a dependent . . . to the extent that such expenses exceed 7.5 percent of adjusted gross income."

Section 213 (d)(1)(A) defines "medical care" as "amounts paid for the diagnosis, cure, mitigation, treatment, or prevention of disease, or for the purpose of affecting any structure or function of the body."

It is very important for the taxpayer to gather the relevant paperwork to support the claimed medical expense deduction for the additional costs from the special diet.

This information is provided to help alleviate the cost of purchasing large quantities of food for an individual who has CF. As you can see, you will have to keep records of food intake and costs. If you do not itemize deductions on your current tax return, or if your federal income tax is already very small, it will probably not be worthwhile to do this. On the other hand, if you decide to do it, this deduction could save you several hundred dollars a year. You must decide whether your food expenses and your specific tax bracket justify taking this deduction. If you are not certain you are eligible for this deduction or have other questions, we suggest that you talk with an attorney, a licensed tax accountant, or an IRS consultant.

*The Cystic Fibrosis Foundation expresses no opinions and makes no recommendations concerning the above information.

http://www.cff.org/UploadedFiles/LivingWithCF/AssistancePrograms/Tax-tips-for-food-expense-deductions.pdf

Two-pronged model could help foil tough cystic fibrosis infections

Two-pronged model could help foil tough cystic fibrosis infections

Hanover, NH--Dartmouth Medical School researchers have devised a novel approach for thwarting the relentless bacterial infections that thrive in the lungs of people with cystic fibrosis (CF), unlocking new possibilities against a tenacious and toxic hallmark of the common genetic disease.

Combining a mainstay antibiotic with drugs to deprive the bacteria of iron, which facilitates their persistent growth, appears to boost infection killing, they found.

Their research, reported in the American Journal of Respiratory Cell and Molecular Biology online and scheduled for publication, builds on the collaborative expertise of DMS microbiology and lung physiology labs studying cystic fibrosis infections.

Cystic fibrosis patients are plagued by infections of the bacteria Pseudomonas aeruginosa. Their mucous-clogged lungs are fertile incubators for the bacteria to breed and cluster in slimy communities called biofilms that become increasingly drug resistant and damaging. Tobramycin, the antibiotic routinely used against the microbes, can control, but not efficiently eliminate Pseudomonas established on CF airway cells.

Last year, the DMS researchers reported that it took far more tobramycin to destroy biofilm pockets than can be delivered to the lungs. Using a surrogate tissue culture system they created to simulate human airways, they determined that up to 10 times the maximum tobramycin dosage was needed. They were also studying iron overload in CF lungs. Airway cells with the CF gene mutation release more iron, and the bacteria depend on that iron to form their resilient biofilms, the investigators discovered.

Now, applying their findings to the clinical front, the team demonstrated that two agents already approved by the Federal Drug Administration to treat acute iron poisoning or overload can enhance the ability of tobramycin against Pseudomonas infection.

"The beauty is that we are mixing FDA-approved drugs-- antibiotics and iron chelators-- to potentiate the effect of tobramycin on biofilm formation," said lead author Dr. Sophie Moreau-Marquis, a research associate. "It's an exciting translational framework that opens the door to potentially treating CF patients, taking the novel model we developed from the lab hopefully to the clinic."

Co-authors of the study are DMS professors Dr. Bruce Stanton of physiology, who heads the laboratory where Moreau-Marquis works, and Dr. George O'Toole of microbiology and immunology.

The research combines two results: "We were first to show iron is definitive for biofilms forming on live human airway cells. And the highest concentration of tobramycin that can reach CF lungs is below what we've shown to be barely enough to eradicate biofilms on airway cells," Moreau-Marquis said.

The team used two FDA-approved iron chelators, deferoxamine and deferasirox, that can remove excess iron from the system by binding to the metal in a process called chelation. To mimic the clinical environment, they stuck to the maximum possible tobramycin dose of 1,000 micrograms per milliliter, mixed with a chelator.

The combination had a dramatic effect: it disrupted the mass of established and highly resistant bacteria in human airway cells by 90 percent and it also prevented formation of damaging biofilms. In contrast, neither an iron chelator nor tobramycin alone had such success.

"We built on the idea that if more iron helps bacteria to grow, maybe taking iron away will help kill them," said O'Toole. "The concept is to reformulate one of these iron chelators to be inhaled with tobramycin, which is already inhalable, to treat the bacteria locally in the lungs."

Still, the team found evidence that a chelator can get into lungs from the bloodstream. Using a permeable support in the lab, they mimicked giving tobramycin to the lung side and a chelator to the blood side and showed that the iron chelator is able to work its way through to lungs.

J Heart Lung Transplant. 2009 Nov 19. [Epub ahead of print]

Factors Indicative of Long-term Survival After Lung Transplantation: A Review of 836 10-Year Survivors.

Weiss ES, Allen JG, Merlo CA, Conte JV, Shah AS.

Division of Cardiac Surgery, Department of Surgery, The Johns Hopkins Medical Institutions, Baltimore, Maryland.

INTRODUCTION: Despite 20 years of lung transplantation (LTx), factors influencing long-term survival remain largely unknown. The United Network for Organ Sharing (UNOS) data set provides an opportunity to examine long-term LTx survivors.

METHODS: We conducted a case-control study embedded within the prospectively collected UNOS LTx cohort to identify 836 adults from 1987 to 1997 who survived >/= 10 years after first LTx. LTx patients within the same era and surviving 1 to 5 years served as controls. Multivariable logistic regression with incorporation of spline terms evaluated the odds of being a 10-year survivor. Two separate models were constructed. Model A incorporated pre-operative, operative, and donor-specific factors. Model B incorporated the factors used in Model A with post-operative covariates. Additional outcomes evaluated included hospitalizations for infection, rejection, and bronchiolitis obliterans.

RESULTS: Of 4,818 LTx patients from 1987 to 1997, 836 (17.3%) survived >/= 10 years with a mean follow-up of 148.8 +/- 21.6 months. Mean follow-up for 1,657 controls was 34.0 +/- 13.9 months. The distribution of 10-year survivors by disease was cystic fibrosis, 170 (20%); chronic obstructive pulmonary disease, 254 (30%); and idiopathic pulmonary fibrosis, 92 (11%). On multivariable logistic regression, significant factors influencing 10-year survival included age

CONCLUSIONS: Examination of a cohort of long-term LTx survivors in the UNOS data set indicates that bilateral LTx and fewer hospitalizations for rejection may portend improved long term-survival after LTx.

Healthcare for Americans

i know quite a # of American citizens who could really use care like this.

bottomline: healthcare is a limited resource. a human is a human, but there has to be ways to allocate scarce resources, such as healthcare.

american citizens deserve abundant and quality healthcare.

only when every american citizen receives the healthcare they require, then we can being considering treating foreign nationals with the scarce resource of American healthcare.



http://community2.myfoxdfw.com/_healthcarewmv/video/801484/78592.html

Tis Best

I found this to be a fantastic gift idea for Christmas. Love it love it love it!

Truely what the holidays should be all about:


http://www.tisbest.org/



The Original Charity Gift Card. TisBest Philanthropy created this fantastic donation gift card for friends, family members, sweethearts, customers and everyone else truly important. We carefully selected the charities featured on our website. There are 250 national nonprofit organizations, and many more local organizations, each of which demonstrates leadership, efficiency, success and innovation in its programs. The recipient spends their TisBest Charity Gift Card by selecting a charity they believe in. A TisBest Charity Gift Card is the perfect gift choice in today's world!

Stem cells may offer alternative to lung transplants

Stem cells may offer alternative to lung transplants

Belgian scientists who used embryonic stem cells to create lung tissue said this technique could provide an alternative to lung transplants for patients with chronic obstructive pulmonary disease (COPD) and cystic fibrosis.

This is the first time it's been shown that embryonic stem cells can be converted into airway epithelial-like cells without the use of specific growth factors or embryoid body formation. The researchers achieved this using an “air-liquid interface” system that mimics the conditions found in an adult trachea. “Efforts will be made to further improve this novel culture protocol, trying to increase the number of differentiated cells or to guide the differentiation into particular cell types by adding certain growth factors to this system,” Lindsey Van Haute, of the department of embryology and genetics at the Free University of Brussels, said in a news release.

She and her colleagues may start with fibroblast growth factors, which play an important role in lung development. Human embryonic stem cells “have the capacity to differentiate in vivo and in vitro into cells from all three germ lineages, making them particularly important in developmental biology, regenerative medicine and in vitro pharmacological studies,” Van Haute said. (Source: HealthDay News)

http://www.tehrantimes.com/index_View.asp?code=208413

Pulmonary outcome differences in U.S. and French cystic fibrosis cohorts diagnosed through newborn screening

Despite lack of universal healthcare, US CF patients fare better than French patients as published in the European journal "Journal of Cystic Fibrosis."


Pulmonary outcome differences in U.S. and French cystic fibrosis cohorts diagnosed through newborn screening.

from PubMed: cystic fibrosis by Walsh AC, Rault G, Li Z, Scotet V, Duguépéroux I, Férec C, Roussey M, Laxova A, Farrell PM,


Pulmonary outcome differences in U.S. and French cystic fibrosis cohorts diagnosed through newborn screening.

J Cyst Fibros. 2009 Nov 17;

Authors: Walsh AC, Rault G, Li Z, Scotet V, Duguépéroux I, Férec C, Roussey M, Laxova A, Farrell PM,

BACKGROUND: A comparison of the longitudinal progression of lung disease in cystic fibrosis patients identified through newborn screening (NBS) in cohorts located in two different countries has never been performed and was the primary objective of this study.

METHODS: The study included 56 patients in Brittany diagnosed through NBS between 1989 and 1994 and 69 similar patients in Wisconsin between 1985 and 1994. The onset and progression of lung disease was radiographically quantified using the Wisconsin Chest X-ray (WCXR) scoring system. A single pediatric pulmonologist blinded to all identifiers scored the films.

RESULTS: Generalized estimating equation analyses adjusted for age, genotype, sex, pancreatic insufficiency, and meconium ileus showed worse WCXR scores in Brittany patients compared to Wisconsin patients (average score difference=4.48; p<0.001). Percent predicted FEV1 was also worse among Brittany patients (p<0.001).

CONCLUSIONS: The finding of milder radiographically-quantified lung disease using the WCXR scoring system, as well as better FEV1 values, may be explained by variations in nutrition, environmental exposures, or healthcare delivery.

Vest studies

Always a debate as to whether CPT or the Vest is better.

First off I will say I firmly believe that European/Canadian/Australian governments don't discuss or offer the Vest because they have socialized medicine and don't wish to pay for it. It's sad and I think it partly contributes to lower median survival rates verus the US.

Secondly, one thing that makes the Vest adventageous is that it is done the same way, consistently, every time. When you have a human performing manual CPT, there is always variation - no two sessions are the same.

Finally, you're never dependent on someone else. I bet everyone who does manual CPT has missed a sessiond to do another person not having time/wanting to/whatever reason being able to do the session for the CFer. You never have that with the Vest (unless you're in Europe with your American Vest and you didn't bring your transformer).

You have one life. One set a lungs. If there's a possibility to slighly imrove your lung function and possibly add years of quality and/or quantity of life, the choice is a no-brainer to me.

Here are a few studies measuring mucus clearance of CPT versus the Vest:



http://www.respirtech.com/pdfs/Hansen.pdf


In a crossover study comparing the volume of mucus cleared using HFCC vs. CPT,
HFCC therapy was shown to be more effective than standard CPT for all outcomes
measured.

Title: Hansen LG, Warwick WJ. High-frequency chest compression system to aid in
clearance of mucus from the lungs. Biomed Instrum Technol 1990;
July/August: 289-294.

Design: Crossover

Method: 5 CF patients received 30 HFCC and 30 professionally administered CPT
sessions.

• Sessions matched for time of day
• Session durations uniform (unspecified)
• Total volume of expectorated sputum collected
• Mean volume with each modality compared
• PFTs compared

Results: Compared to 30 CPT treatments, 30 HFCC treatments showed:

• Significantly more mucus clearance with HFCC (3.3cc/HFCC session
vs. 1.8 cc/ CPT session [p<0.001])
• Improved lung function
• Improved ventilation
• No adverse events

HFCC was shown to be more effective than CPT for every outcome measure




http://www.respirtech.com/pdfs/Kluft.pdf


This large randomized controlled crossover trial compared high frequency chest
compression (HFCC) with professionally administered chest physiotherapy (CPT) in 29
cystic fibrosis (CF) patients hospitalized with acute pulmonary exacerbations. Sputum
weight (wet and dry) was a proxy for efficacy. Results showed nearly three times greater
sputum clearance in the HFCC group.

Title: Kluft J, Beker L, Castagnino M, Gaiser J, Chaney H, Fink R. A comparison of bronchial
drainage treatments in cystic fibrosis. Pediatr Pulmonol 1996; 22: 271-274.

Design: A prospective, randomized controlled, cross-over

Method: Twenty-nine hospitalized CF patients with acute pulmonary exacerbations received
randomized treatment with HFCC and CPT

• Two days with each therapy over a 4-day period
• Three 30 minute therapy sessions/day
• Expectorated secretions collected during each 30 minute therapy session
• Twelve specimens per patient
• Wet and dry weights determined gravimetrically
• Means and standard deviations ( X + SD) based on 348 total sputum samples

Results:
Weight CPT/PD (X + SD) HFCC (X+ SD) P VALUE
Wet weight (g) 2.86 + 4.0 6.76 + 9.7 0.001
Dry weight (g) 0.26 + 0.45 0.74 + 2.4 0.01

• HFCC is effective: Dry sputum weights were nearly threefold greater than those
expectorated with professionally administered CPT
• No adverse effects were observed
• Patient tolerance and acceptance were high


http://www.respirtech.com/pdfs/Warwick.pdf

In a long-term study comparing chest physiotherapy (CPT) to high frequency chest
compression (HFCC) in cystic fibrosis (CF) patients, 94% showed positive improvements for percent predicted forced vital capacity (FVC) and forced expiratory volume in one minute (FEV1) after two years of HFCC therapy. Most showed clinical improvement. The long - term FVC and FEV1 gains shown in this study are unprecedented.

Title: Warwick WJ, Hansen LG. The long-term effect of high-frequency chest
compression therapy on pulmonary complications of cystic fibrosis.
Pediatr Pulmonol 1991; 11:265-271.

Design: Retrospective

Method: FEV1 scores recorded during 2 years of CPT were compared with scores
during 2 years of subsequent HFCC in sixteen CF patients with mild to severe
lung disease.

• CPT 1 - 4X daily for a mean of 23.2 months (range: 14-27
months)
• 1 - 4X daily HFCC for a mean of 21.6 months (range:7-26 months)
• 30-minutes daily minimum for 5 minutes at each of 6 frequencies
• Individual patient therapy times ranged from 30-240 minutes daily
• Concomitant coughing and huffing techniques used

Results: Two-sided t-test analysis:
• Slopes more positive for FVC and FEV1 during HFCC therapy compared
with manual CPT
• Significance level for both FVC and FEV1: P < 0.001





http://www.respirtech.com/pdfs/Anbar.pdf

This short-term evaluation of the effect of HFCC on pulmonary function compared with
chest physiotherapy (CPT) or alternative therapies in 54 CF patients showed significant
improvements in FEV1 after an average 3 months of HFCC treatment.

Title: Anbar RD, Powell KN, Iannuzzi DM. Short-term effects of ThAIRapy® Vest on
pulmonary functions of cystic fibrosis patients. Am J Respir and Crit Care Med
1998; 157 (Suppl 3): A130.

Design: Retrospective Chart Review

Method: Pulmonary function data gathered by retrospective chart review was analyzed for
54 CF patients meeting inclusion criteria:

• Age > 5 years (average = 17 years)
• Compliant HFCC therapy for at least 6 months
• Average HFCC use = 19 minutes/day (+13 minutes)

Prior use of CPT or not
○ 61% used chest physiotherapy (CPT)
○ 39% had NOT used CPT

Post - HFCC PFT’s were compared with best PFT scores obtained 0-6 months
pre-HFCC

Results: Best PFT results:

12 – 18 mo pre - HFCC FEV1 (+SD) 78+26 FVC (+SD) 95+24
0 – 6 mo pre - HFCC FEV1 (+SD) 76+26 FVC (+SD) 97+24
0 – 6 mo post - HFCC FEV1 (+SD) 82+29 FVC (+SD) 101+26

• FEV1 values improved an average of 8% overall

• FEV1 values improved an average of 7 % in patients using CPT prior to
HFCC
• FEV1 values improved an average of 11% in patients using non-CPT
therapies prior to HFCC
• No adverse events were reported

Arch Dermatol. 2009 Nov;145(11):1296-9.

Aquagenic wrinkling of the palms in cystic fibrosis: comparison with controls and genotype-phenotype correlations.

Berk DR, Ciliberto HM, Sweet SC, Ferkol TW, Bayliss SJ.

Department of Internal Medicine and Pediatrics, Division of Dermatology, Washington University School of Medicine and St Louis Children's Hospital, Campus Box 8123, 4921 Parkview Place, St Louis, MO 63110, USA. dberk@dom.wust.edu

OBJECTIVE: To determine the prevalence of aquagenic wrinkling of the palms (AWP) in patients with cystic fibrosis (CF) compared with control patients, and evaluate for genotype-phenotype correlations.

Since its first description over 30 years ago, AWP has frequently been anecdotally associated with CF, but this association has not been confirmed in a rigorous prospective case-control study.

DESIGN: Blinded comparison.

SETTING: The CF and dermatology clinics at St Louis Children's Hospital.

PARTICIPANTS: Forty-four individuals with CF from a CF clinic and 26 controls from a dermatology clinic. Intervention Participants were tested for AWP using 3 minutes of water immersion with room-temperature tap water.

Main Outcome Measure The degree of AWP was scored from 0 (no wrinkling) to 4 (severe wrinkling) by 3 blinded physicians. F

or genotype-phenotype correlations, patients with CF were divided into those homozygous for the DeltaF508 mutation and those with other genotypes.

RESULTS: The mean AWP score of the CF group was significantly higher than the mean score of the control group (1.5 vs 0.6; P < .001). Patients with CF who were homozygous for the DeltaF508 mutation (n = 27) had significantly higher scores than patients with CF who were not homozygous for the DeltaF508 mutation (n = 17) (1.7 vs 1.1; P = .02). The 17 patients with CF who were not homozygous for the DeltaF508 mutation still had higher scores than the control group (1.1 vs 0.6; P = .03). There was no correlation between sweat chloride concentrations measured at the time of diagnosis and AWP score.

CONCLUSIONS: Our results confirm the association between AWP and CF. Among patients with CF, greater AWP occurs in those who are homozygous for the DeltaF508 mutation.

Diabetes Care. 2009 Nov 16. [Epub ahead of print]

Diabetes as a Determinant of Mortality in Cystic Fibrosis.

Chamnan P, Shine BS, Haworth CS, Bilton D, Adler AI.

1. MRC Epidemiology Unit, Institute of Metabolic Science, Cambridge.

Background: Diabetes is increasingly common in cystic fibrosis (CF), but little exists describing its influence on mortality. Using national UK data, this study documents diabetes-specific mortality rates, estimates the impact of diabetes on survival, and estimates population attributable fractions.

Methods: This retrospective cohort study identified 8,029 individuals aged 0-65 years from the UK CF Registry (1996-2005). 5,892 patients were included in analyses of mortality rates and 4,234 in analyses of risk factors. We calculated age-adjusted mortality rates using Poisson regression, standardized mortality ratios using the population of England and Wales, and relative risks using proportional hazards modeling.

Findings: During 17,672 person-years of follow-up, 393 subjects died. The age-adjusted mortality rate was 1.8/100 person-years (95% CI 1.6 to 2.0).

The age-adjusted mortality rates per 100 person-years were 2.0 (CI 1.8 to 2.4) in women and 1.6 (95% CI 1.4 to 1.9) in males, and 4.2 (95% CI 3.4-5.1) in individuals with diabetes vs 1.5 (95% CI 1.3 to 1.7) in those without diabetes.

Independent risk factors for death included diabetes (hazard ratio, 95% confidence interval, 1.31 (1.03 to 1.67), female sex (1.71, 1.36 to 2.14) plus poorer pulmonary function, lower body mass index, B. cepacia infection, absence of S. aureus infection, allergic bronchopulmonary aspergillosis, liver disease, prior organ transplantation, and corticosteroid use.

Interpretation: Individuals with CF die earlier with diabetes, which, if delayed or better treated, might reasonably extend survival, and merits testing.

PMID: 19918014 [PubMed - as supplied by publisher]

CF Foundation is Halfway to Receiving $6 Million Matching Gift

CF Foundation is Halfway to Receiving $6 Million Matching Gift

November 16, 2009

The CF Foundation announced today it is halfway to receiving a $6 million matching gift.

In July, two very generous CF families announced they will match every major gift donation of $10,000 or more the Foundation receives through December 31, 2009.

The CF Foundation has already secured $3 million in major gifts and pledges.

However, to ensure the Cystic Fibrosis Foundation receives the full $6 million match, we will need to raise $3 million more by December 31.

These critical funds will support the search for new treatments and a cure for cystic fibrosis.

For more information, please contact Gina Schewe, Senior Director of Major Gifts at (301) 907-2506 or rschewe@cff.org.

Published on Science Blog (http://www.scienceblog.com/cms)

Penn study finds that antioxidant found in vegetables has implications for treating cystic fibrosis

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Penn study finds that antioxidant found in vegetables has implications for treating cystic fibrosis

By BJS

Created 11/16/2009 - 18:30

PHILADELPHIA -- Scientists at the University of Pennsylvania School of Medicine discovered that a dietary antioxidant found in such vegetables as broccoli and cauliflower protects cells from damage caused by chemicals generated during the body's inflammatory response to infection and injury. The finding has implications for such inflammation-based disorders as cystic fibrosis (CF), diabetes, heart disease, and neurodegeneration.

Through cell-culture studies and a synthesis of known antioxidant biochemistry, Zhe Lu, MD, PhD , Professor of Physiology, Yanping Xu , MD, PhD , Senior Research Investigator, and Szilvia Szép , PhD, postdoctoral researcher, showed that the antioxidant thiocyanate normally existing in the body protects lung cells from injuries caused by accumulations of hydrogen peroxide and hypochlorite, the active ingredient in household bleach. These potentially harmful chemicals are made by the body as a reaction to infection and injury. In addition, thiocyanate also protects cells from hypochlorite produced in reactions involving MPO, an enzyme released from germ-fighting white blood cells during inflammation. They published their finding this week in the Proceedings of the National Academy of Sciences. Lu is also an Investigator of the Howard Hughes Medical Institute.

"Dr. Lu's work throws new light on how the genetic defect underlying CF leads to the lung illnesses that are the leading cause of death," said Bert Shapiro, Ph.D., who oversees membrane structure grants at the National Institutes of Health's National Institute of General Medical Sciences (NIGMS). "His team's findings suggest that the lungs of people with the disease are more susceptible to the damaging effects of cellular oxidants. While the idea is tantalizing and creative, further testing is needed to confirm it."

The research team demonstrated that in three additional cell types used to extend their ideas to other inflammation-related conditions -- cardiovascular disease, neurodegeneration, and diabetes -- thiocyanate at blood concentrations of at least 100 micromolar (micromoles per liter) greatly reduces the toxicity of MPO in cells, including those lining blood vessels. Humans naturally derive thiocyanate from some vegetables and blood levels of thiocyanate in the general population vary from 10 to 140 micromolar.

This comparison raises the possibility, the authors point out, that without an adequate dietary supply of thiocyanate, hypochlorite produced by the body during inflammation would cause additional collateral damage to cells, thus worsening inflammatory diseases, and predisposing humans to diseases linked to MPO activity, including atherosclerosis.

Connection to CF

For over a decade Lu and colleagues have been exploring the inner workings of ion channels and how this knowledge relates to the pathology of such diseases as CF. The CF disease originates from mutations in the CF transmembrane conductance regulator (CFTR) protein, an ion channel protein in the cell membrane commonly thought to transport mainly chloride ions. It has, however, remained a mystery why a defect in a chloride-transporting channel leads to cystic fibrosis, a disease with exaggerated inflammation in both the lungs and the digestive system.

Lung injuries inflicted by excessive inflammation and recurring infection cause about ninety percent of CF patients' symptoms and mortality. Although known as a chloride channel, CFTR also conducts thiocyanate ions, important because, in several ways, they can limit potentially harmful accumulations of hydrogen peroxide and hypochlorite, chemicals produced by the body to fight germs.

In CF patients, there is also a high incidence of diabetes, partly caused by damage to the pancreas. Type 2 diabetes is also associated with higher levels of MPO in the blood. The researchers found that the MPO-caused injuries to pancreas cells and endothelial cells used in their experiments can be greatly reduced by as little as 100 micromolar thiocyanate. Their finding raises the possibility that MPO, in the absence of adequate thiocyanate, contributes to diabetes.

In the cell-based experiments, thiocyanate at concentrations below 100 micromolar did not eliminate hypochlorite accumulation and did not fully protect against MPO toxicity. Conceivably, inadequate thiocyanate levels would aggravate MPO-produced injuries in patients suffering from inflammatory diseases, surmise the authors.

Links to Other Diseases

In other studies, MPO activity has been linked to lung cancers among smokers and also implicated in neurodegenerative diseases. Intriguingly, people with congenital MPO deficiency are less likely to develop cardiovascular diseases. The research team found that MPO-caused injuries to nerve cells, as well as to blood vessel-lining endothelial cells, can be greatly reduced by 100 micromolar thiocyanate.

Genetic defects in the CFTR predispose CF patients' lungs to excessive inflammation entangled with recurring lung infection. Defective CFTR channels would be expected to result in lower thiocyanate concentrations in the affected regions within the respiratory, as well as the digestive systems, leaving tissues inadequately protected from accumulated hydrogen peroxide and overproduced hypochlorite.

Conceptually, delivering thiocyanate directly to the digestive and respiratory systems might be a therapy for CF disease, propose the researchers. As for the general population, individuals with low blood levels of thiocyanate may be at risk for chronic injuries by MPO, predisposing them to inflammatory or inflammation-mediated diseases. Many investigators have proposed developing drugs that specifically inhibit MPO-catalyzed hypochlorite production to combat these diseases, but natural thiocyanate not only decreases MPO-catalyzed formation of hypochlorite but also rapidly, once it is made, neutralizes it.

"In light of the obvious implications of this protective action of thiocyanate against the cell-damaging effect of MPO activity with regard to both CF disease and general population health, my colleagues and I will vigorously investigate the potential health benefit of thiocyanate," says Lu. He emphasizes though, "until the research community acquires a better understanding of both positive and negative impacts of thiocyanate on human health, it would be unwise for anyone to self-administer thiocyanate because like many other chemicals, thiocyanate has adverse side effects at improper doses and/or under inappropriate conditions."

The research was funded by NIGMS and the Howard Hughes Medical Institute.

This release can be found at: http://www.uphs.upenn.edu/news/News_Releases/2009/11/antioxidant-cystic-fibrosis/ [1]

Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the University of Pennsylvania School of Medicine (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $3.6 billion enterprise.

Penn's School of Medicine is currently ranked #3 in U.S. News & World Report's survey of research-oriented medical schools, and is consistently among the nation's top recipients of funding from the National Institutes of Health, with $267.2 million awarded in the 2008 fiscal year.

Penn Medicine's patient care facilities include:

• The Hospital of the University of Pennsylvania ? the nation's first teaching hospital, recognized as one of the nation's top 10 hospitals by U.S. News & World Report
• Penn Presbyterian Medical Center ? named one of the top 100 hospitals for cardiovascular care by Thomson Reuters
• Pennsylvania Hospital ? the nation's first hospital, founded in 1751, nationally recognized for excellence in orthopaedics, obstetrics & gynecology, and behavioral health.

Additional patient care facilities and services include Penn Medicine at Rittenhouse, a Philadelphia campus offering inpatient rehabilitation and outpatient care in many specialties; as well as a primary care provider network; a faculty practice plan; home care and hospice services; and several multispecialty outpatient facilities across the Philadelphia region.

Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2008, Penn Medicine provided $282 million to benefit our community.

Rev Port Pneumol. 2009 Sep-Oct;15(5):899-921.

[Lung diseases and gastro-oesophageal reflux disease]

[Article in Portuguese]

Pereira JC.

Médico Tisiologista do Serviço de Atendimento Especializado da SMS -Belford Roxo, Médico do CRA -DIP do Hospital Municipal Nelson de Sá Earp e do Programa de Controle da Tuberculose da SMS - Petrópolis - Rio de Janeiro - Brasil. jclaudiobarroso@oi.com.br

Gastro -oesophageal Reflux Disease is a consequence of pathological reflux from stomach to oesophagus. Whenever the refluxed contents extended beyond the oesophagus itself, is called Extraoesophageal Reflux Disease. The author proposes a review about pulmonary disorders and gastroesophageal reflux. Previously, it is evaluated in an abridged way, the concepts of each diseases and after that, in a systematic form, it is discussed the prevalence of gastro -oesophageal reflux in lung diseases, all the mechanisms studies and the impact of gastro -oesophageal treatment on lung disorders. The author concludes that is undeniable the link between Gastro -oesophageal reflux and lung diseases and further reaserch is mandatory in order to corroborate this association.

PMID: 19649547 [PubMed - indexed for MEDLINE]

Diurnal Variations in Human Pulmonary Function

Thanks to Skye for bringing this article to my attention!


Diurnal Variations in Human Pulmonary Function




Bottomline: The difference in the forced expiratory volume in 1 second (FEV1) between the noon (12:00–12:59 pm) and afternoon (4:00–4:59 pm) intervals was 17.6% (P<0.01).


Abstract

Pulmonary function has circadian modulations. Variations in human pulmonary function during the daytime hours (diurnal variations) remain to be well characterized. Discerning these variations will contribute to better understanding the relationship between biorhythms and lung physiology and to improving clinical management of pulmonary diseases.

The aim of this study was to determine the magnitude of pulmonary function variability during the usual daytime hours in a population of patients referred for pulmonary function testing. Diurnal fluctuations of human pulmonary function were examined by studying retrospectively a study population of 4,756 individuals with performed pulmonary function tests. We found the lowest and highest spirometric values in the 12:00–12:59 pm and 3:00–4:59 pm time intervals respectively. The difference in the forced expiratory volume in 1 second (FEV1) between the noon (12:00–12:59 pm) and afternoon (4:00–4:59 pm) intervals was 17.6% (P<0.01). F

urthermore, the highest values of diffusing capacity of the lung for carbon monoxide [DLCO] and alveolar volume [Va] were identified in the 8:00–8:59 am time interval. These findings, identifying a model of diurnal variations of pulmonary function in individuals referred for pulmonary function testing, are of interest for better understanding lung physiology and human circadian rhythms and may have clinical value in managing lung disorders.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2592592/

Systemic, nasal and oral live vaccines against Pseudomonas aeruginosa

Vaccine. 2009 Oct 31. [Epub ahead of print]

Systemic, nasal and oral live vaccines against Pseudomonas aeruginosa: A clinical trial of immunogenicity in lower airways of human volunteers.

Bumann D, Behre C, Behre K, Herz S, Gewecke B, Gessner JE, von Specht BU, Baumann U.

Junior Research Group "Mucosal Immunology", Department of Immunology, Hanover Medical School, Hannover, Germany.

Vaccination against Pseudomonas aeruginosa is a desirable, yet challenging strategy for prevention of airway infection in patients with cystic fibrosis. We compared the formation of antibodies in lower airways induced by systemic and mucosal vaccination strategies.

We immunised 48 volunteers in six vaccination groups with either a systemic, a nasal, or four newly constructed oral live vaccines based on attenuated live Salmonella (strains CVD908 and Ty21a), followed by a systemic booster vaccination. All vaccines were based on a recombinant fusion protein of the highly conserved P. aeruginosa outer membrane proteins OprF and OprI as antigen. While systemic and mucosal vaccines induced a comparable rise of serum antibody titers, a significant rise of IgA and IgG antibodies in the lower airways was noted only after nasal and oral vaccinations.

We conclude that nasal and oral OprF-OprI vaccines are promising candidates for development of antipseudomonal immunisation through inducing a specific antibody response in the lung.

PMID: 19887136 [PubMed - as supplied by publisher]

Mol Pharm. 2009 Nov 3. [Epub ahead of print]

Partial Correction of Cystic Fibrosis Defects with PLGA Nanoparticles Encapsulating Curcumin.

Cartiera MS, Ferreira EC, Caputo C, Egan ME, Caplan MJ, Saltzman WM.

Cystic fibrosis (CF) is a common life threatening genetic disease (incidence: ~1 in 2500 live births). CF is caused by mutations in CFTR, a chloride channel involved in epithelial secretion of fluid and electrolytes. The most common mutation entails the deletion of a phenylalanine in position 508 that causes protein misfolding and abnormal CFTR processing. The DeltaF508 mutation accounts for approximately 70% of all CF alleles and about 90% of CF patients carry at least one copy of DeltaF508 CFTR.

Curcumin, a natural constituent of Curcuma Longa (turmeric spice), is a non-toxic low-affinity SERCA (Sarco (Endo)plasmic Reticulum Calcium ATPase) pump inhibitor thought to permit DeltaF508 CFTR escape from the ER. The compound has been shown to be capable of correcting the defect in cell lines and mice expressing F508 CFTR. In this work, poly-lactic-co-glycolic acid (PLGA) nanoparticles encapsulating curcumin were synthesized and used to treat two different CF mouse strains in an effort to correct the defects associated with CF by improving bioavailability of the compound, which has previously been a challenge in treatment with curcumin.

Our results suggest that oral administration of PLGA nanoparticles encapsulating curcumin enhances the effects of curcumin therapy in CF mice, as compared to delivery of non-encapsulated curcumin.

PMID: 19886674 [PubMed - as supplied by publisher]

Threw Another Clot

Well, my PICC was feeling tender the past few days and I thought it would be best to get an ultrasound just to play it safe.

And what do you know.

Clot.

Bleh. It's a superficial clot this time as opposed to a DVT that I had in January, but still.

What's a girl to do on blood thinners when she has a history of coughing up blood? Could this get any scarier?

Is anyone out there a serial clotter?


I don't think I'm being rough on my PICC arm - no lifting weights; no repetitive motions; no carrying heavy things.

I'm going to see if I can get a specialist to give an opinion on what may be causing this. It could of course just be "me" but I certainly haven't had this issue in years past.

If anyone has any advice, experience, etc I would be grateful. Thanks guys!

Lung Tissue Generated From Human Embryonic Stem Cells

Lung Tissue Generated From Human Embryonic Stem Cells

ScienceDaily (Nov. 4, 2009) — Scientists in Belgium have successfully differentiated human embryonic stem cells (hESC) into major cell types of lung epithelial tissue using a convenient air-liquid interface. The technique, published in BioMed Central's open access journal Respiratory Research, could provide an alternative to lung transplants for patients with lung injury due to chronic pulmonary disease and inherited genetic diseases such as cystic fibrosis.

Lindsey Van Haute and colleagues from the Department of Embryology and Genetics at the Free University of Brussels (Vrije Universiteit Brussel) demonstrated for the first time that hESC could be converted into epithelial-like cells in human models. Van Haute and colleagues assessed hESC differentiation using an air-liquid interface system that mimicks the conditions found in an adult trachea. Expression data of lung-specific biomarkers from quantitative real-time RT-PCR supported the differentiation into lung epithelial cells. Furthermore, the combination of these mRNA expression results, as well protein expression, secretion and localization showed the presence of the major cell types of lung epithelial tissue.

This study demonstrates that hESC can differentiate into lung epithelial-like tissue without specific growth factors or embryoid body formation. The air-liquid interface on a porous membrane combined with low serum is sufficient to prime the cells to form an airway epithelial-like tissue.

"Efforts will be made to further improve this novel culture protocol, trying to increase the number of differentiated cells or to guide the differentiation into particular cell types by adding certain growth factors to this system," says Van Haute. The team may start with fibroblast growth factors, which are important in the developing lung, to test whether their addition to the culture medium influences the differentiation pattern.

Van Haute continues, "hESC have the capacity to differentiate in vivo and in vitro into cells from all three germ lineages, making them particularly important in developmental biology, regenerative medicine and in vitro pharmacological studies. hESC lines carrying a monogenic disease affecting the lung, such as cystic fibrosis, are available. This novel technique can be used on these affected hESC lines and provide researchers with putatively clinically relevant tools to develop in vitro models for these diseases."



http://www.sciencedaily.com/releases/2009/11/091104191823.htm

Inhaled Mannitol Improves the Hydration and Surface properties of Sputum in patients with Cystic Fibrosis

Chest. 2009 Oct 31. [Epub ahead of print]
Inhaled Mannitol Improves the Hydration and Surface properties of Sputum in patients with Cystic Fibrosis.

Daviskas E, Anderson SD, Jaques A, Charlton B.

Royal Prince Alfred Hospital, Respiratory and Sleep Medicine, 11 West, Missended Rd, Camperdown, Sydney, New South Wales, Australia, 2050, 61 2 9515 7410, 61 2 95158196, daviskas@med.usyd.edu.au.

BACKGROUND: The airway mucus in patients with cystic fibrosis (CF) is dehydrated and adhesive, and accumulates in the airways resulting in chronic inflammation, infection and progressive loss of lung function. Inhaled mannitol improves mucus clearance and, when administered over 2-weeks, it improves lung function in CF (Jaques A et al. CHEST 2008;133:1388-1396). The changes in the physical properties of sputum after a 2-week treatment with mannitol were investigated in the same CF subjects. M

ETHODS: Sputum was collected before and at the end of the 2-week treatment period from 28 CF subjects who participated in the double blind crossover study. Mannitol or placebo 420 mg was inhaled twice daily over 2-weeks. The solids content, surface tension, contact angle and viscoelasticity was measured.

RESULTS: Two-week treatment with mannitol reduced the solids from 7.3+/-3.0 to 5.7+/-3.0% (p=0.012), surface tension from 83.1+/-7.2 to 78.6+/-8.0 mN/m (p<0.039) and contact angle from 52.4+/-7.7 to 47.9+/-7.3 degrees. There was no significant change in the viscoelastic properties of sputum (p>0.1). Placebo treatment had no significant effect on the sputum properties. The change in solids content correlated with the change in both FEV(1) (r(s)=-0.78, p=0.004) and FEF(25-75) (r(s)=-0.80, p=0.003) and the % change in surface tension and contact angle correlated with the % change in the FEV(1) (r(s)=-0.73, p=0.012 and r(s)=-0.63, p=0.03 respectively) in these subjects.

CONCLUSION: Treatment with inhaled mannitol over 2 weeks improved the hydration and surface properties of sputum in patients with CF. This effect was sustained and correlated with airway function changes.

Inspire Pharmaceuticals, Inc. announced today patient enrollment is complete in Denufosol

DURHAM, N.C.--(Business Wire)--
Inspire Pharmaceuticals, Inc. (NASDAQ: ISPH) announced today patient enrollment
is complete in three of its late-stage clinical trials.

"We are pleased to be executing on our strategic plan with the achievement of
these patient enrollment milestones in the clinical development programs for
denufosol, PROLACRIA and AZASITE®,as this places us in a position to have
top-line results from all our late-stage clinical programs within 18 months. We
would like to thank the dedicated clinical investigators, study coordinators and
patients who participated in our trials as well as the Cystic Fibrosis
Foundation and its affiliates for raising awareness of the importance of
participating in clinical trials," stated Benjamin R. Yerxa, Ph.D., Executive
Vice President and Chief, Research and Development.

Denufosol Tetrasodium for Cystic Fibrosis

Inspire announced today that TIGER-2, the Company`s second Phase 3 pivotal
clinical trial (Trial 08-110) with denufosol tetrasodium inhalation solution for
the treatment of cystic fibrosis (CF), has completed patient enrollment. TIGER-2
is a 48-week trial comparing 60 mg of denufosol to placebo, administered
three-times daily by jet nebulizer, in a targeted 450 CF patients. The Company
expects to have top-line results from TIGER-2 in the first quarter of 2011.

"We are excited that patient enrollment in TIGER-2 is complete. This is an
important step toward bringing this potential new treatment to cystic fibrosis
patients," said Robert J. Beall, Ph.D., President and CEO of the Cystic Fibrosis
Foundation. "Denufosol`s novel approach to treating the underlying ion channel
defect in CF lung disease makes it a promising therapy, and we look forward to
the results from this trial."


About Denufosol Tetrasodium

Denufosol tetrasodium is a first-in-class receptor-mediated chloride channel
activator that addresses the underlying ion transport defect in the lungs of
patients with cystic fibrosis (CF). Denufosol is designed to enhance airway
hydration and mucociliary clearance through receptor-mediated mechanisms that
increase chloride secretion, inhibit sodium absorption and increase ciliary beat
frequency. These integrated pharmacological actions are important to restoring
airway clearance, maintaining lung function, and potentially delaying the
progression of CF lung disease. Denufosol is targeted as an early intervention
therapy for CF lung disease. This product candidate has been granted orphan drug
and fast-track review status by the U.S. Food and Drug Administration (FDA) and
orphan drug status by the European Medicines Agency (EMEA).

About Inspire

Inspire is a biopharmaceutical company focused on researching, developing and
commercializing prescription pharmaceutical products for ophthalmic and
pulmonary diseases. Inspire`s goal is to build and commercialize a sustainable
portfolio of innovative new products based on its technical and scientific
expertise. The most advanced compounds in Inspire`s clinical pipeline are
PROLACRIA™ (diquafosol tetrasodium ophthalmic solution) 2% for dry eye and
denufosol tetrasodium for cystic fibrosis, which are both in Phase 3 development
and AZASITE® (azithromycin ophthalmic solution) 1% for blepharitis, which is in
Phase 2 development. Inspire receives revenues related to the promotion of
AZASITE for bacterial conjunctivitis, the co-promotion of ELESTAT® (epinastine
HCl ophthalmic solution) 0.05% for allergic conjunctivitis and royalties based
on net sales of RESTASIS® (cyclosporine ophthalmic emulsion) 0.05% for dry eye.
For more information, visit www.inspirepharm.com.


Inspire Pharmaceuticals, Inc.
Investor Contact:
Jenny Kobin, 919-941-9777, Extension 219
VP, Investor Relations and Corporate Communications
or
Media Contact:
Cara Amoroso, 919-941-9777, Extension 266
Manager, Corporate Communications

I was a CFer coughing blood for Halloween

Well just as I was about to put on my fab Kate Goselin wig for my Halloween outing (my BF was metally preparing himself for the onslaught of black eyeliner that would soon form his side burns) I felt a nice pop in my lungs and out came blood.

Lots.

I hadn't seen this much since 2007.

Joy.

So 911 it was and off to the ER.

Luckily things calmed down in a few hours and when all was said and done it was prob 1/3 of a cup of blood. Probably not that much to you hemo vets, but scary for me. As my doc says, 1/3 cup can turn into a full cup in a blink of an eye.

So, today, Wednesday right? I'm loosing track of time with the hospital transfers and atavan PICC insertions :) today my pulm will look at the CT scan an see if we can do some exploring with the interventional radiologist.

Never fun to think about but I've had too many of these bleeds to not attempt to fix things.

I'll keep you posted on any developments!