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Monday, March 28, 2011

Inhaled PDE5's treat CF

Never realized the plan was to nebulize cialis or levitra - always thought we would just take them as a pill. So interesting....

Expert Opin Investig Drugs. 2011 Mar 24. [Epub ahead of print]

Inhaled phosphodiesterase type 5 inhibitors for cystic fibrosis: a new therapy for systemic disease?

University of Medicine and Pharmacy "Gr.T.Popa" Iasi, Department of Internal Medicine II-Pulmonary Disease, Pulmonary Disease University Hospital, 30 Dr I Cihac Str, 700115 Iasi, Romania +40 232 
239408 ; +40 232 270918 ; sabina.antonela.antoniu@pneum.umfiasi.ro.


Cystic fibrosis is a rare disease characterized by abnormalities in chloride and sodium transmembrane transportation due to various mutations in the cystic fibrosis transmembrane regulator (CFTR) gene, F508del being the most commonly found. Corrective therapies for this defect are currently under investigation and PDE5 inhibitors such as sildenafil or vardenafil were found to improve CFTR activity in vitro as well as in vivo. This paper evaluates a study investigating the effects of inhaled PDE5 inhibitors in an animal model of F508del cystic fibrosis, demonstrating that in this new formulation, such compounds are also able to improve CFTR function. Such results support the further development of this therapy for a systemic disease such as cystic fibrosis, provided several issues are addressed.
PMID: 21434839 [PubMed - as supplied by publisher

Using Tobra in the eFlow

Pediatr Pulmonol. 2011 Apr;46(4):401-8. doi: 10.1002/ppul.21376. Epub 2010 Dec 30.

Higher Tobramycin concentration and vibrating mesh technology can shorten antibiotic treatment time in cystic fibrosis.

Physiology and Experimental Medicine, Research Institute of Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada. allan.coates@sickkids.ca.


Poor adherence to recommended therapy in cystic fibrosis (CF) is often because of the time demands of therapy. Tobramycin (TOBI®, 300 mg at 60 mg/ml) inhaled from the PARI LC PLUS® nebulizer requires about 20 min. 

This study determined if equivalent levels of pulmonary deposition could be achieved in shorter time using 1.5 ml of 100 mg/ml tobramycin solution delivered by an investigational eFlow® nebulizer. 

Sixteen males with stable CF, 8 children and 8 adults, and an FEV(1)  > 45% predicted inhaled both preparations on two occasions with (99m) Tc-DTPA added to the tobramycin. Blood samples were taken for quantification of tobramycin in the serum. The PARI LC PLUS® delivered 45.4 (39.3-51.6), mean and 95% CI, mg to the lungs in 17.0 ± 2.5 min (mean ± SD) with serum levels of 1,089 ± 388 µg/L. 

The investigational eFlow® delivered 46.3(40.3-51.7) mg in 4.0 ± 1.0 min with blood levels of 909 ± 458 µg/L. Only the time of delivery was significantly different with P < 0.0001 (paired t-test). Tolerability of the treatment was comparable for both inhalation regimes, but the shorter treatment was preferred by all patients.

 These results demonstrate the possibility of delivering equivalent levels of tobramycin much faster into the lungs of CF patients when using eFlow®, a very efficient electronic nebulizer. Pediatr Pulmonol. 2011; 46:401-408. © 2010 Wiley-Liss, Inc.
Copyright © 2010 Wiley-Liss, Inc.

Sunday, March 6, 2011

A Comparison of Amount and Speed of Deposition Between the PARI LC STAR(®) Jet Nebulizer and eFlow(®) Nebulizer

A Comparison of Amount and Speed of Deposition Between the PARI LC STAR(®) Jet Nebulizer and an Investigational eFlow(®) Nebulizer.

Divisions of Nuclear Medicine and Respiratory Medicine, Hospital for Sick Children Research Institute, University of Toronto , Toronto, Canada .


Abstract Background: The potency and physical properties of many of the drugs used in the treatment of cystic fibrosis necessitates the use of nebulization, a relatively time-consuming pulmonary delivery method. Newer, faster, and more efficient delivery systems are being proposed. 
The purposes of this study was to compare the length of time it took to deliver the equivalent of normal saline nebulized for 10 min in a PARI LC STAR(®) nebulizer to that of an investigational PARI eFlow(®). 

Methods: Six normal adults inhaled a 4-mL (36-mg) charge volume of saline from the LC STAR(®) or a 2.5-mL (22.5-mg) charge volume from the investigational eFlow(®). The saline was mixed with (99m)Tc-DTPA to allow two-dimensional imaging. The inhalation was preceded by a xenon equilibration scan to allow more accurate separation of deposition into central and peripheral lung regions. 

Results: The investigational eFlow(®) delivered 8.6 ± 1.0 mg, approximately 90% of the lung dose compared to the LC STAR(®), 9.6 ± 1.0 mg, but did in less than half the time (p < 0.02 for both). There were no differences in central versus peripheral distribution for either device. Conclusions: In conclusion the investigational eFlow(®) was both faster and more efficient than the LC STAR(®).

The cystic fibrosis sufferer who took off around the world

The cystic fibrosis sufferer who defied doctors and took off around the world... with a backpack full of life-saving drugs

Last updated at 8:29 PM on 28th February 2011
For as long as I can remember, I have wanted to travel the world – and forget for a while that I have cystic fibrosis (CF).

It is a disease that I was born with and it affects the lungs and digestive system, causing them to become clogged with thick, sticky mucus. I will die from it, although I don’t know when. I am 24 – the average life expectancy is 35.

About 8,500 people in the UK have CF and, so far, there’s no cure. Five babies are born every week with the condition. But I live a pretty normal life. I work in IT, I’m an avid cricket fan and have played since my early teens.
Cavan Arrowsmith
Down Under: Cavan Arrowsmith with his girlfriend Claire in Sydney on his trip to remember
I spend time with my girlfriend, Claire. I also have to take medicine morning and night to manage my condition.

As a child, being told you aren’t going to live for many years is hard to understand. Now I have to be realistic, and know my limits, but I am also determined to live a fulfilled life.
My aim was a ten-month trip to the US, Asia and Australia to prove I could do it, and to inspire others.

It took months to organise and there were a few medical dramas along the way, but in the end even they turned out to be part of the adventure . . .
Cavan Arrowsmith
Hot and dirty: Cavan struggled on the India leg of his trip because the country's environment was not good for his health
FEBRUARY 28, 2010
It’s a little after 5am when my dad, John, my 67-year-old nan, Irene, and Claire pile into Dad’s car for the short trip from his home in Stourbridge, West Midlands, to Birmingham Airport and the big send-off.

My 120-litre red-and-black backpack is stuffed to bursting, but not because I need lots of clothes. Half the pack contains a three-month supply of medicine. I have to take five tablets to help my digestion, and Creon capsules that contain a pig enzyme that helps break down food.
I also have two inhalers with drugs that help keep my airways open and free from inflammation, and a nebuliser (a machine that turns medicines into vapour that I can then inhale through a mask) to deliver a daily antibiotic that helps to tackle chest infections.
There is another nebuliser that helps break down the mucus in my lungs, reducing the amount I cough.
Majestic: Cavan and friends at the Grand Canyon
Majestic: Cavan and friends at the Grand Canyon
On top of these I need a daily calcium supplement and multivitamins as I can’t absorb nutrients properly.

Oh, and there are more tablets such as emergency antibiotics. The other half of my pack has all the usual stuff such as walking boots, my laptop and sleeping bag.

I told my doctor about my plans and he said as I was well, it was a good time for me to travel. Dad and Claire hug me goodbye, leaving me alone with Gordon Clarke, my best friend from primary school, who is joining me for the whole journey.

After a few final waves we’re through security and on our way. Next stop: San Francisco.

Our flight goes via Frankfurt, where we join Robert Black and Matthew Smith, friends from Birmingham City University. Gordon and I will come back to the UK, briefly, after three months to replenish my medical supplies.

Rob and Matt will be with us for the America leg and then head home. We allow a week to see San Francisco but just two days in, my nebuliser breaks.

We have to order a spare part from my hospital consultant back home in Birmingham, who arranges for the manufacturers to send out the part. It takes a week to arrive.

But we make the most of the time to see all the city’s famous sights, such as the Golden Gate Bridge, cable cars, the ferry ride to Alcatraz, and Chinatown.

Cavan Arrowsmith
Eastern promise: Cavan and his friend Gordon conquer the Great Wall of China

We’re finally on the move again and from San Francisco we head inland to Las Vegas in our rather cramped camper van. It’s the best our budget can manage. There’s one double bed at the back, which two of us share, and one single bed in the kitchen.

There’s also a double bed above the driver’s area. We call this the ‘penthouse’ and take turns to sleep there every fourth night. My friends have never treated me any differently because I have CF. But I can’t be as carefree as they are.

When Matt comes down with a chest infection, I have to make sure I sleep as far away from him as possible. Catching a cold can mean hospital for me. I am also supposed to eat 5,000 calories of food a day, which is double the normal recommendation for a man.

This is because my body is constantly fighting infection, which burns up huge amounts of energy. I can’t miss meals and I am always hungry. Luckily, there are no shortage of food stops on a US road trip.


After Vegas, and then the Grand Canyon, we head to Scottsdale, Arizona, and carry on across America, stopping in Texas, Tennessee and then New York, where we watch Ricky Gervais at Madison Square Garden.

It reminds me of home and how much I miss Claire. We have known each other since the age of five, growing up together as friends before becoming a couple in secondary school.
Meeting the locals: Cavan with members of the Black Hmong hill tribe in Vietnam
Meeting the locals: Cavan with members of the Black Hmong hill tribe in Vietnam
My CF is part of her life, too. I have been hospitalised five times, mainly for chest infections, for about two weeks each time. The last time, Claire came back to visit me from Portsmouth where she was studying law.

We plan to move in together when I get back, and settle down. I want children, although not right away. We have discussed the fact that I might not be around for ever, and when my children are teenagers I don’t want to be so unwell that I can’t be part of their lives.

But I’m hoping by then there will be a cure. And it is all the more reason to stay fit and active, as exercise really helps reduce infection.

With Central Park, the Statue of Liberty and Fifth Avenue behind us, we head north to Boston and our final stop on this particular leg.

MAY 20

We are back in Birmingham so I can restock with medicine. My consultant said I needed to come to see him only if I wasn’t well, and I feel fine. Better than that. It’s so fantastic to see Claire.

We have to wait for Gordon’s India visa to come through. In the meantime, I begin filling my bag with boxes of tablets, inhalers . . . My stepmum, Joanne, and sister, Lucy, 17, come to see me off.

Next time I see Dad, I’ll be 24, which is amazing really as when I was born the doctors told him I wouldn’t live beyond my teens.

One of the gang: Cavan on a group camping trip on Fraser Island in Australia
One of the gang: Cavan on a group camping trip on Fraser Island in Australia

Bombay is shocking. We stay in a cheap hotel 60 miles from the city centre with cockroaches on the floor and no proper loos. It’s hot and dirty and a constant challenge to find unopened, bottled water to clean the mouthpieces of my nebuliser. 

The air is dusty and I cough a lot. Parts of India are really beautiful, particularly the Taj Mahal, and Goa is gorgeous but it’s always in the back of my mind that this place isn’t good for me.
Leaving at the end of June does not come soon enough.

We’re in Beijing, struck by the vastness of Tiananmen Square and everything that’s in it, including Mao’s Mausoleum. We’ve heard the best place to access the Great Wall is from Mutianyu, about 90 minutes out of the city, and we’re not disappointed.

There’s a cable car to the top but Gordon and I walk up instead. It’s about 800 steps, which takes 40 minutes. I beat Gordon up there. With regular long walks and cricket, I’m actually pretty fit by any standards.

My lung function – a measure of how well the lungs are working – is average, not for CF patients but for anyone of my age, although when I have a chest infection this drops dramatically.
Our thighs burn from the effort but it really is worth it. The views from the top are stunning.


From Beijing we head to Shanghai. It’s humid, something I have to avoid. Damp, warm air in my lungs is a breeding ground for bacteria.

Gordon and I stay in an eight-bed dorm and there are a lot of sniffles going round. I start to feel unwell.

We press on to see the Terracotta Army at Xi’an. I’m feeling pretty terrible and I suspect I have picked up a cold as I am coughing a lot, but we continue to Hong Kong, by train, and then fly to Hanoi, Vietnam.

I know if I seek medical help it will be admitting defeat, so I take emergency antibiotics as a last resort.
Brave face: Cavan on a drip while being treated at Bangkok Hospital
Brave face: Cavan on a drip while being treated at Bangkok Hospital

By now we’re at Nha Trang, a beautiful city on Vietnam’s coast, but I’m feeling worse and the cold has become a full-on chest infection.

One of the biggest obstacles to this trip was finding insurance. I was turned down by 15 companies before the Cystic Fibrosis Trust put me in touch with Ageas, which covered me for £470. Gordon paid just £120.

I need treatment and though it takes them five days, the insurers find me a hospital in Bangkok, so we board a bus. I’m in hospital for two weeks while the insurance company organises accommodation for Gordon.

Finding high-calorie food isn’t that easy, and noodle soup just doesn’t cut it. So every day Gordon brings a McDonald’s milkshake, burgers and fries, and then spends the rest of the day with me as I slowly recover.


Rested and back to health, I am discharged and we fly to Perth. In hospital I was running on a treadmill with the physiotherapist every day, so I feel great. And now in Australia I’m out on the beach, swimming and attempting to surf. Being outdoors really agrees with me.
Within a few weeks Gordon and I are broke, so we both get jobs in call centres and work for the next two months.


It’s my 24th birthday and, like all my birthdays, it’s a real reason to celebrate. I’m planning to live a long time. But I am aware that 50 years ago babies born with CF often didn’t live beyond a year.

Claire and two friends, Laura and Karl, have flown out and I am over the moon. We hire a car and drive to Adelaide, Melbourne and then Sydney, where we climb the Harbour Bridge. I would move here in a heartbeat.


Gordon and I arrive back to a freezing Birmingham. I’ll be for ever grateful to him for helping me achieve something I’ve held in my heart for so long and to the people who stepped in along the way to keep me on track. I’m home.

Job done. The sky really is the limit.

●Cavan is raising money for the Cystic Fibrosis Trust. www.justgiving.com/cavanarrowsmith

Read more: http://www.dailymail.co.uk/health/article-1360955/The-cystic-fibrosis-sufferer-defied-doctors-took-world--backpack-life-saving-drugs.html#ixzz1FnanVQ9D

Association between genotype and pulmonary phenotype in CFers

J Cyst Fibros. 2011 Feb 25. [Epub ahead of print]

Association between genotype and pulmonary phenotype in cystic fibrosis patients with severe mutations.


BACKGROUND: Despite numerous studies a clear relationship between genotype and pulmonary phenotype has not been established within the group pancreatic insufficient cystic fibrosis (CF) patients. We studied the relationship between class I and class II mutations and pulmonary function in Swedish patients with known CFTR functional classification.
METHODS: 170 CF patients with two class II mutations, 18 with two class I mutations and 78 with a combination of class I and II mutations were included in the study. Spirometry was performed when patients were in an optimal clinical condition.
RESULTS: Patients with two class I mutations had lower lung function (FEV(1) and FVC) compared to the group with either a combination of class I and II mutations or two class II mutations.
CONCLUSION: CF patients carrying two class I mutations risk developing more severe lung disease compared to patients with at least one class II mutation.
Copyright © 2011 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.