Having ”suicidal ideation” is associated with being a smoking young asthmatic – a key risk factor for having severe asthma?   Leave a comment

Having ”suicidal ideation” is associated with being a smoking young asthmatic – a key risk factor for having severe asthma?

I saw an abstract today on pubmed, linking “suicidal ideation” and smoking in young adults with asthma. This study originates in Korea, and is published locally, but is certainly interesting also from a global perspective.

Suicidal ideation is “a common medical term for thoughts about suicide, which may be as detailed as a formulated plan, but without the suicidal act itself”. The Korean colleagues have gathered data from a very large cohort (>75000 individuals), and identified a large cohort of asthmatic smokers. Indeed, the data showed that smoking was more common in asthmatic youths, than in non-asthmatics, and there was a significant interactions between asthma and suicidal ideation with cigarette use behavior http://1.usa.gov/mdVkCm . The authors conclude that “particular attention should be paid to the awareness of health risks of cigarette smoking and mental health problems among asthmatic adolescents”.

These data certainly support the research line in our research centre, looking at personality traits in relation to adherence to asthma medication http://bit.ly/lxQIOr and http://bit.ly/fZu7WL. Personality, psychology, psychopathology, health behavior and adherence to medication are certainly key factors in some patients with severe asthma. An interesting older paper from the Leiden group with Elisabeth Bel and colleagues http://bit.ly/jYnQr1

Posted May 28, 2011 by Jan Lötvall in Uncategorized

New England Journal of Medicine paper on asthma, suggesting that remodeling is a result of airway narrowing, not the other way around…   Leave a comment

New England Journal of Medicine paper on asthma, suggesting that remodeling is a result of airway narrowing, not the other way around…

It is generally suggested that airway wall remodeling in asthma is a result of active inflammatory processes. In the current study in the prestigious New England Journal of Medicine http://bit.ly/kLYWwT , investigators from Southampton suggest that induction of bronchoconstriction by itself can induce some signs of remodeling, without a parallel process of enhanced inflammation occurring. What the investigators did, was to induced airflow obstruction by provocation with allergen, which induces significant eosinophilic inflammation, or with methacholine, which does not induce inflammation. Control groups were given either a bronchodilator or the vechicle for the provocation (saline). Importantly, the challenges were given repeatedly, which is not normally done in clinical research. Different profiles of lung function changes were observed after the challenges, with a late response being induced by allergen, and no late response observed after methacholine.

The key finding reported is that both allergen- and methacholine provocation increased subepithelial collagen-band thickness, to a similar degree. However, the measured changes were really small in both instances, but the photomicrographs shown are impressive. The statistics was based on µg change in “collagen-band” thickness, and on average the change was reported to be around 2µm for each of the challenges. Baseline thickness in asthma has been reported to be around 10µm, but variable between patients. In the current paper, it was reported to be on average 7.47-10.76 in the different groups. Thus, any observed change was in the region of 20%.

The authors conclude that “Bronchoconstriction without additional inflammation induces airway remodeling in patients with asthma. These findings have potential implications for management.” Subepithelial fibrosis has indeed been suggested to be one sign of remodeling in asthma, but its role to induce airway narrowing has been questioned. Furthermore, perhaps other challenges, such as dry air isocapnic hyperventilation or exercise should be tested, to determine whether any bronchoconstricting event can have such results.

I was disappointed that no “primary variable” was reported in the paper. Further, the statistics were allowed to be “one way”, which is unusual in medical research. New England Journal of Medicine usually is tough on those issues…

In summary, yes, the usual. More research is required to confirm these findings…

Posted May 28, 2011 by Jan Lötvall in Uncategorized

What is severe asthma, a separate disease or a mixture of diseases? And how should it be defined?   2 comments

What is severe asthma, a separate disease or a mixture of diseases? And how should it be defined?

Bel and colleagues recently published a review on the “diagnosis and definition of severe asthma”, as a consensus from the Innovative Medicine Initiative/ in Thorax: http://bit.ly/knWXTZ . Also recently, Bousquet and collagues defined different types of “severe asthma”, as “uncontrolled asthma which can result in risk of frequent severe exacerbations (or death) and/or adverse reactions to medications and/or chronic morbidity (including impaired lung function or reduced lung growth in children)” / The publication in Journal of Allergy and Clinical Immunology: http://bit.ly/iDFBxG.
They continue by dividing severe asthma into three separate subgroups including

1) untreated severe asthma,
2) difficult-to-treat severe asthma,
3) treatment-resistant severe asthma (for which asthma control is not achievable with intense therapy).

Do these publications help the scientific community in understanding “severe asthma”. In a way, they are helpful to improve the nomenclature, but obviously they are using different wordings (for example “treatment resistant” vs “refractory” – which may be similar but not exactly the same). And are they based on scientific data? The answer to that is – yes and no…

Firstly, we do not have a common definition of severe asthma, although clinicians around the world understand that they have a group of patients that are really difficult to manage, because their asthma just does not get better. In fact, there are multiple reasons for that happening. Firstly (and perhaps most commonly), patients with asthma are very often not taking their medication as prescribed: http://bit.ly/iZUv88 and http://1.usa.gov/lv1i4N. Secondly, there is a subgroup of patients which simply have a severe intrinsic disease, that is difficult to control with normal medication, as proposed by Bel and colleagues http://bit.ly/knWXTZ . Thirdly, a large group of individuals with severe asthma have so called “co-morbid diseases”, which includes obesity, severe rhinitis and chronic rhinosinusitis http://bit.ly/jqrFke and http://bit.ly/kzIuLd . We have recently shown that a series of different risk-factors exist for severe asthma in a population-based sample.

The West Sweden Asthma Study sent out 30000 questionnaires to a random population in the region, had a 62% response rate, and identified a prevalence of asthma of 8.5% in this stable and normally distributed population. Further, the prevalence of SEVERE ASTHMA, as defined by individuals having multiple daytime symptoms, was found to be approximately 2%: http://respiratory-research.com/content/10/1/94. The risk factors of having this definition of “severe asthma” was:

1) Symptoms of rhinitis
2) Signs of Chronic rhinosinusitis
3) Female sex
4) Exposures to dust and fumes
5) Obesity (BMI>30)
6) Heredity of asthma and allergy.

Thus, co-morbidites (point 1, 2 and 4) were clear risk factors. Hereditary components, presumably related to intense intrinsic disease, were only related to two of the risk factors (points 3 and 6). Otherwise, exposures are also obvious important (point 4). Details are found here: http://bit.ly/jBgoyX and http://bit.ly/dEvEsh .
Thus, this definition of severe asthma (multi symptom asthma) identified THREE individual causes of severe asthma

1) Comorbidities (Severe rhinitis, Chronic rhinosinusitis and Obesity)
2) Herediatary components (family history and/or female sex)
3) External exposures.

Is severe asthma one disease? The answer is without question NO. It is not. We have to look at the facts, and follow the evidence, to really fully understand whatever we wish to call “severe asthma”. We should follow the advice of Bertrand Russel as referenced in my blog posting from earlier today: http://bit.ly/jt0Fvi

Posted May 28, 2011 by Jan Lötvall in Uncategorized

The core of science and politics, wise words by Bertrand Russel   Leave a comment

There is a lot of politics in science, and arguing about this that and the other. We scientists see it all the time, and perhaps we sometimes forget the core of science: Finding the Truth. And only the Truth… And when we find the truth, there is not much to argue about… As long as we agree with it…

And in politics, there is one core principle that is important. Live in peace!

These two core principles of humanity were well described by Bertrand Russel in this old interview, when asked “what advice would you like to give to future generations”:

Thank you Maneck for directing me to this video.

In the exosome field we are searching for consensus to be able to establish the truth. By using crowdsourcing. Are we trying to bridge science and politics, to avoid conflict. Maybe. And to find the truth and provide opportunities to communicate that truth.
From my previous blogpostings:
http://bit.ly/kOLMAv
http://bit.ly/kSn7lM

Finding consensus through crowdsourcing, starting with the small exosome community   Leave a comment

To find consensus on exosome methodology and nomencalture, a 48 question long questionnaire was developed over the last one-two months. It is now “live” using surveymonkey, and seems to be working very well. We have a close to 10% response rate already an hour after sending out the invitation by e-mail…

If you are an exosome researcher and have not received the invitation to participate, just e-mail me (jan.lotvall@gu.se).

In the future, I am sure we will develop similar questionnaires for larger crowds and bigger tasks. This is kinda cool.

News on the results of this specific crowdsourcing activity can be followed on the facebook page of the community: http://www.facebook.com/home.php?sk=group_171229582921487

Posted May 27, 2011 by Jan Lötvall in Uncategorized

Thoughts on how to bring the exosome and microvisicles communities together   1 comment

There is a lot of interest in the development of communication platforms in the field of exosomes. Long term, I am sure the best way is to create an association/academy in the field. Those attending the IWE in Paris in January agreed it was the right way forward. Now, how can that be done?

This has been communicated with a few people in the field, and lets call it a “DRAFT strategy to for the creation of a global exosome- and microvesicles community”

Goal:
1) Create a World Exosomes and Microvesicles Society (maybe WEMS)
2) Create a yearly World Exosomes and Microvesicles Meeting (maybe WEMM)
3) Provide a multi-level platform through which exosomes and microvesicles scientists liaise and communicate among each other, including scientific meetings, schools, web-sites and other interactive web-based tools. The establishment of a society based scientific journal should be considered.

Approach:
1) Create a single yearly world meeting, which should be the platform for communicating recent science in the exosomes and microvesicles field.
2) Join all researchers in the field to come to a consensus on core principles of methodology, using crowdsourcing techniques (for example to create a position for how to distinguish exosomes and microvesicles) ONGOING
3) Bring in all research in the field to come to a consensus on nomenclature using crowdsourcing techniques (should the naming of the vesicles be based on size, source or biological effect, or other aspects)

Benefits:
1) The fields of exosomes and microvesicles is relatively small, and need to collaborate more efficiently to achieve faster progress
2) The annual meeting becomes a natural platform for the scientific community to meet
3) The annual meeting becomes a natural platform for commercial entities to interact with the scientific community
4) The community becomes stronger when forces are joined
5) Competitive commercial meetings are avoided, surplus of meetings go to the community, not to private enterprises

Possible time plan:
1) April May 2011; Join forces to plan a World meeting (ongoing)
2) Deciding of the timing of world meetings (plus minus two weeks), possibly during first half of 2012
3) May 2011; Crowdsourcing to come to a consensus on methodology. ONGOING
4) Summer 2011; Crowdsourcing to come to a consensus on nomenclature in the microvesicles and exosomes fields. BEING PLANNED
5) Summer 2011; establish an interim board for the World Society
6) Summer 2011; establish a scientific programme committee for the 2012 meeting
7) August 2011; invite the whole community to become members of the society
8.) Autumn 2011; create two publications reporting on the positions/consensus on a) methodology, b) nomenclature
9) Autumn 2011; launch of a society website
10) Abstract submission deadlines for the WEMM in January 2012
11) April 2012 WEMM (GOTHENBURG SWEDEN)
12) April 2012 WEMS General Assembly, formal meeting establishing the society, establishing a formal board of the society
13) April 2012, launch of a possible journal (not everyone is for this step)
14) May 2012 Publication of abstracts in the putative web-based journal
15) June – august 2012; likely publication time for position papers/consensus reports based on the crowdsourcing activity performed in 2011 (in own journal if our decision is to create that)
16) April 2012 Meeting (placed in US, New York possible location)

Long-term visions:
1) The society flourish and a good collaborative atmosphere is created
2) The community stands stronger in a competitive scientific environment
3) Formal scientific collaborations are easier to set up when the community meets
4) Juniors can easier find new labs to pursue postdoctoral studies in the same field
5) Meeting-associated incomes can be used for the benefit of the community (journals, websites, stipends, travel grants etc)
6) The society could create one year international fellowships when funds are sufficient
7) Other outcomes

Any comments exosome friends?

PS, just for clarification: I have no personal wish to lead this, but can help in some of the steps proposed

Posted May 17, 2011 by Jan Lötvall in crowdsourcing, exosomes

finding consensus on exosome methodology   1 comment

I have just sent this out to a large group of exosome researchers, to try to find consensus on how to deal with differences in opinion on how to purify exosomes. I hope to get a strong response.

Dear Exosome Friends,

You are copied into this e-mail (blinded copy) because you have expressed interest in exosomes, and/or because you attended the 2011 IWE in Paris. Some of you may receive duplicates, simply because I had two different lists of e-mails that were only partly overlapping.

Firstly, I would like to remind you to mark your calendars for next year’s International Workshop on Exosomes, IWE, which will be held in Gothenburg Sweden 18-21 April 2012. We have booked a very nice venue, with a large lounge for posters and interactions, beyond the lecture that will accommodate a significantly greater audience than we had in Paris. We will do our very best to arrange the most enjoyable experience possible, including the scientific programme as well as all social aspects. Specifically, we will try to arrange a special meeting evening, with a pleasant programme. We have also been able to pre-book hotels at very good rates indeed, and we can promise a very enjoyable meeting. For info on Gothenburg, go to: http://www.goteborg.com/en/?epslanguage=en . The meeting has no web-site yet, but we will develop one in good time.

On another note, I think it would be very timely to develop a consensus on different aspects of methodology and characterization of exosomes in biological fluids and culture medium, which I also mentioned in a discussion session during the IWE in Paris. There are several ways of approaching such questions, one being placing four to seven “super-experts” in a room, and let them sit there until they have decided what their consensus is on the topic at hand. An alternative approach is to “crowdsource”, to see where the consensus lies, but using a much larger community. Such techniques are starting to be utilized in the development of consensus reports/guidelines for clinical treatments of disease, and so far it seems that the “average” opinion often ends up as being “reasonable”, based on current knowledge. In Medicine, this approach increases the possibility of also those that are less inclined to publically express opinion, to actually influence recommendations.

We are therefore suggesting that we should try the “crowdsourcing” approach to reach a consensus also in the exosome field. My impression is that there are wide differences on how methods of purifying exosomes are pursued, for example, and different opinions on such details can have profound influence on the possibilities to publish the research. Also, it would be much easier to compare work, if the exosomes were extracted in similar ways in similar experiments. The aim of this activity would thus be to establish a “reasonable” definition on how to characterize exosomes, based on current knowledge and opinion, including methods to isolate and describe exosomes. We are therefore reaching out to each and every one that we could identify in the exosome community to ask you to be involved. Please therefore consider the following:

1) Are you willing to participate in this project in a coordinating group/ writing group, that will finalise the questionnaire, and author any publication at a later stage? If so, respond to this e-mail to both me and Margareta, renaming the e-mail “exosome coordination”.
2) Are you willing to participate in a “test round” of a questionnaire that the coordinating group develops? Again, e-mail me and Margareta, and rename the e-mail “exosome test round”.
3) I strongly encourage every single one to participate in the final questionnaire, to really influence the future of exosome research. The questionnaire will of course be web based, and will give the possibility of written comments, that can be signed or not. Any comments will be retained in the public domain adjacent to any publication, probably as web-supplements. Expect the questionnaire to be circulated in a month or so, depending on how well the questionnaire development goes.

If we are successful in this process, we could really develop a strong “position” of the whole exosome community, which will make it much easier for any editor of any scientific journal to understand what defines exosomes, not accepting inappropriate nomenclature or flawed techniques. We certainly have to accept slightly different protocols depending on material, origin and focus of the research.

The principles of crowdsourcing can be found here: http://en.wikipedia.org/wiki/Crowdsourcing

Please feel free to call me or contact me by e-mail, if you have any concerns, thoughts or suggestions. I hope you will be as positive about this approach as I am.

Kind regards
Jan

Exosome meeting in 2012, Gothenburg, Sweden   5 comments

Exosome meeting in 2012

We are very excited to host the 2012 International Workshop on Exosomes in Gothenburg, Sweden April 18-21. The intention is to include any science involving exosomes, but also to invite those working with microvesicles to contribute, to more clearly find ways to distinguish differences in the biology of these fundamentally different vesicles released by cells.

Should the meeting be focused on specific aspects of these vesicles? Should we have a “topic”, perhaps focusing on exosomes and microvesicles in immunology or in cancer or in general cell biology? Personally I think the field of exosomes is still quite small and is only starting to grow, why we should avoid too much focus in 2012. I hope this exosome meeting really can bridge over research field, and create new collaborations between researchers that otherwise would not meet.

Maybe a new community will be created?

I can already now say that a special effort will be made to create good and interactive poster sessions during the meeting.

 

 

Posted March 19, 2011 by Jan Lötvall in exosomes, gene therapy, medicine, RNA, science

asthma in athletes needs to be treated correctly   3 comments

http://www.expressen.se is writing that WADA is planning to possibly take away the classification of formoterol as restricted drugs for athletes. That is probably a wise approach. EAACI will still pursue its plan to discuss such decisions, since asthmatics may have risk of taking long-acting beta-2-agonists only without concomitant use of inhaled glucocorticoids (http://bit.ly/gLBxAL ). The question is thus not so simple. Asthma must be treated correctly, otherwise athletes may be at risk.

Expressens current comments:

http://www.expressen.se/sport/2.701/langdskidor/1.2346078/bjorgens-medicin-bort-fran-dopinglista

Posted February 27, 2011 by Jan Lötvall in Allergy, asthma, EAACI, medicine, science, Treatment, Uncategorized

Bjorgen is not taking doping   Leave a comment

http://www.expressen.se

An article is mentioning that the world champion cross-country skier Marit Björgen is taking formoterol-containing asthma medication. Björgen has asthma, and has been properly diagnosed. It is absolutely appropriate to take such medication if you have asthma, and there is in fact NO evidence that formoterol is helping performance, and in fact this pharmacological entity should be taken off the doping list.

The EAACI  Executive Committee has today approved to rapidly do a task force to discuss the doping classing of formoterol and other asthma drugs, and will soon come with feedback on how such drugs should be classed and dosed in athletes with asthma.

http://www.expressen.se/sport/2.701/langdskidor/1.2345554/jag-har-papper-och-allting-pa-min-sida

Posted February 26, 2011 by Jan Lötvall in Allergy, asthma, EAACI