Asthma - Science topic

You can use this study if you still do not calculate the sample size:

Licorice is used to treat dermatitis, liver swelling, mouth sores, and a variety of other ailments, but there is no scientific evidence to back up most of these claims.

Repeated spirometry and repeated attempts is to achieve 3 acceptable FEV1s and FVC and choose the highest FVC in restricted disease and highest FEV1 in obstructive disease , this will give a good information

يمكنك مراجعة اهل الاختصاص

No, antihistamines do not improve bronhial asthma. Some benefits could be present in rhinitis, asociated to asthma.

Dear Désirée Larenas-Linnemann

These links might be useful to find out, have a look:

1. https://www.who.int/ncds/management/Protocol3_1_Asthma.pdf

2. https://www.mayoclinic.org/diseases-conditions/asthma/in-depth/asthma-treatment/art-20044284

3. https://link.springer.com/article/10.1186/s13223-020-00472-8

Kind Regards

Qamar Ul Islam

I can mention one study with taxometric analysis in parastic disease:

Anshu Malhotra et al. Taxometric analysis of helminths of marine fishes 1.Pedunculacetabulum spinatum n. Sp., from chlorinemus mandetta and wenyonia rhincodonti n. Sp., from Rhincondon typus. Journal of parastic diseases, 2011:35(2):222_9.

DOI. 10.1007./s12639_011_0049_0

Plz try above site.

Hello Muhammad,

Sure, you could do this sort of thing. I think that your case for a causal relationship would be better served by using, say, 2018 data for CO2 emission, and 2019 data for asthma prevalence, however.

The question is, what is the smallest level at which you could collect reliable data for both variables? At the country level, a state level, a district/township/municipality level? The higher the level of aggregation, the greater the likelihood that observed relationships would not mirror very well what you would find if you had the luxury of tracking the two variables at the individual person level. Sociologists refer to this phenomenon as the ecological fallacy.

Good luck with your work.

Hi, sure they do.

However, your observation may be not reliable (they rub their noses, and feel irritated). The most objective measurement of the in vivo lung function is performed by whole-body plethysmography. You measure the airway reactivity (as fold increase of enhanced pause (Penh) values for the increasing concentration of methacholine relative to baseline. Please refer to the manuscript, as attached

Asthma patients (in most of the cases) already had previous history of symptoms suggestive of asthma and are mostly aware of their specific aural or predisposing factors with likely family history and no exposure or contact with someone with flu like symptoms. One might find it difficult to differentiate the type of respiratory distress as a sign. However, I don't expect to see fever, anosmia, headache or throat pain in a clear cut asthmatic case.

Acetate or propionate don't have any direct role in treatment of any disease and in this case Asthma. These can be used as a supplement as they can help the gut microflora, or pH balance, however, they do not have any other effect/property which could directly be involved in the treatment.

The following links may be of some help:

Best

Yes. Thank dear Victoria Blinkhorn. Your information is useful.

Seems to be effective one in asthmatic patients.

Dear all, this document provides actual information on 1,8-cineole as an anti-inflamatory cure. My Regards

Interesting - https://www.webmd.com/lung/covid-allergies.

Allergies - a kind of Antigen - Antibody reaction ( Hypersensitivity Reaction ) - Increases the body defence mechanism .

The invent of the vaccine of COVID-19 seems to remain after the virus is infected by a large audience. It is understood that the strongest resistance against COVID-19 will be realized by loading vitamin C.

Parsa - it depends what you mean by low impact factor. As you are investigating behaviour and tobacco consumption - then it is a good idea to target 'health education' journals i.e. Health Education, Health Education Journal, Health Education Research - as well as health pomotion i.e. Health Promotion International, Global Health Promotion etc.

Reality is that up to 500,000 deaths occur due to seasonal influenza every-year (1) despite availability of a vaccine. Over 17 million deaths occur every year due to Ischemic heart disease (2).

1.

2. https://www.who.int/health-topics/cardiovascular-diseases/#tab=tab_1

Hello Joseph Shenekji Joseph,

You can do these manually in Excel but online tools are available too For eg. "SNP_tools" is an MS Excel add-in for analysis of genotype data.

You can follow these steps:

1. Determination of Allelic and Genotype frequencies for cases and controls.

2. Hardy-Weinberg equilibrium check by chi-square test

3. Association with the disease using the chi-square test.

4. Normality check by Shapiro-Wilk test

5. Compare the demographic variables like age by t-test (parametric) or Mann Whitney test (no-parametric) between cases and controls

6. If you have a clinical variable such as disease severity to correlate go for Pearson (parametric) or Spearman (non-parametric) correlation test.

I generally do this kind of analysis in SPSS, a software where you can perform statistical analysis after uploading the dataset. Softwares like R, MedCalc and GraphPad Prism are also there. R is an open-source application. You might also like to consult a biostatistician at your university who will scrutinize the properties of your dataset and tell you what tests fit best.

Best wishes,

@

Absolutely should be given just because they reduce interstitial inflammation as a part of COVID 19 pathogenicity.

Please take a look at this useful RG link.

That was really really helpful Garry McDonald

I appreciate that

Please also see the following PDF attachments.

Sorry, I dont know, so I should follow the colleagues responses to obtain more informations.

Kindly see the following RG links and PDF attachments.

Dear Samuel,

I am definitely interested in exploring fungal diagnostics in resource-limited settings, as I am from such a country. Additionally, fungal asthma has not been explored in my country, Namibia.Therefore, I would like to be part of this study.

You can contact me on the following email address: cdunaiski@nust.na

Thank you for the opportunity. I look forward to this collaboration.

Kind regards,

Cara Mia Dunaiski

Unfortunately I haven't had any experience in this but absolutely different serotypes active immune system,s pathways in different way so seek for pathways and check with your goals.

Regards.

@ Rawan Shaker

The asthma affects more than 2 million people in Saudi Arabia, and majority of them have uncontrolled asthma with their quality of life adversely being impacted. The reasons for prevalence of asthma in Saudi Arabia include change in lifestyle, socioeconomic status, dietary habits and allergens, dust, tobacco smoke, sandstorms, and industrial and vehicular pollutants. Please take a look at the following RG links for more details.

Thanks!

If the patient has antibodies against HEV and HDV, it is reasonable to assume that he has been infected with these virus. If he had also been infected with HBV, one would expect antibodies against this virus. Raised IgG indicates an ongoing infection, but not with what. AFAIK, it is usual to determine circulating virus antigen and nucleic acid to ascertain how active the infection is. In addition, liver enzymes can be determined in serum, to measure liver damage. Whether a liver biopsy is indicated, only an experienced internist can tell.

Could be an example for Hickam's dictum: "Patients can have as many diseases as they darn well please".

Hello, Inhaled corticosteroid as the initial maintenance therapy, ideally started within 2 years of symptom onset, is highly effective in both children and adults and across various degrees of asthma severity. If asthma is not controlled, the choice of subsequent add-on therapies differs between children and adults.

We've successfully used the Newcastle Asthma Knowledge Questionnaire in a research context for parents of children with asthma

1. What are 3 main symptoms of asthma?

2. One in ten children will have asthma at some time during their childhood.

3. Children with asthma have abnormally sensitive air passages in their lung.

4. If one child in a family has asthma then all of his/her brothers and sisters are likely to have asthma as well.

5. Most children with asthma have an increase in mucus when they drink cow’s milk.

6. Write down everything that you know may trigger an asthma attack.

7. During an attack of asthma the wheeze may be due to muscles tightening in the wall of the air passages in the lungs.

8. During an attack of asthma, wheeze may due to swelling in the lining of the air passage in the lung.

9. Asthma damages the heart.

10. Write down two treatments (drugs) for asthma that are commonly used on a daily basis.

11. Which asthma treatments (drugs) are useful during an asthma attack?

12. Antibiotics are an important part of treatment for most children with asthma.

13. Most children with asthma should not consume dairy products.

14. Allergy shots cure asthma.

15. If a person dies from an asthma attack, this usually means that the final attack must have begun so quickly that there was no time to start any
treatment.

16. People with asthma usually have ‘nervous problems’.

17. Asthma is infectious (i.e. you can catch it from another person).

18. Inhaled medications for asthma (e.g. Ventolin inhalers) have fewer side effects than tablets or syrups.

19. Short courses of oral steroids (such as prednisolone) usually cause significant side effects.

20. Some asthma treatments (such as Ventolin) damage the heart.

21. A five year old child has an asthma attack and takes two puffs from a Ventolín® inhaler (a metered-dose inhaler). After five minutes there is no improvement. Give some reasons why this may have happened.

22. During an asthma attack that is being treated at home, your child needs to use an inhaler with a space chamber (or mask) every two hours. He is getting better but after two hours he is having difficulty breathing. Since the child is not getting worse, it is OK to continue giving the treatment every two hours.

23. Write ways in which one can help prevent an asthma attack during exercise.

24. Children with asthma become addicted to their asthma drugs.

25. Swimming is the only suitable sport for asthmatics.

26. Parental smoking may make the child’s asthma worse.

27. With appropriate treatment most children with asthma should be able to lead a normal life with no restrictions on activity.

28. The best way to measure the severity of a child’s asthma is for the doctor to listen to the child’s chest.

29. Asthma is usually more of a problem at night than during the day.

30. Most children with asthma will have stunted growth.

31. Children with frequent asthma symptoms should take preventive drugs.

Example Answers

True

When we challenged allergic ships that were sensitive to egg protein, the asthma attacks occurred in two patterns - one immediate, and one delayed like 20 min. later. The only measure we found that was consistent with the clinical findings was the early rise and the late rise of plasma thrombospondin (TSP), which was released from activated platelets. And, the platelet activation was induced by the interleukin and cytokine release. Perhaps you may look at the pattern of the onset of asthma attacks after allergen challenges.

Shih-Wen Huang, MD

We have used EDN for serum and sputum samples and it should work in BAL as well. And I would assume other eosinophil marker such as EPX, ECP or MBP should work as well. In human tissue staining of eosinophils EPX works very well (see )

MPO activity is frequently used as surrogate for neutrophils. I'm not aware of a similar assay for EPX.

Having a quick look I would chose for EPX ELISA because companies of known quality provide such ELISAs e.g. https://www.lsbio.com/elisakits/mouse-eosinophil-peroxidase-epx-elisa-kit-sandwich-elisa-ls-f7707/7707?trid=247.

The International Study of Asthma and Allergies in Childhood (ISAAC) has data from 1994-2012 of bigger international study of asthma. The questionnaire included a question of asthma exacerbation.

From the " The ISAAC page data archive:

ISAAC datasets have now been deposited in an openly accessible data archive. Individual- and centre-level data and documentation from ISAAC Phases One, Two and Three are now accessible at the following webpage: http://discover.ukdataservice.ac.uk/catalogue?sn=8131.

This is the link of ISAAC: http://isaac.auckland.ac.nz/

You could try to obtain the data and good luck.

Best wishes from Castelló (Spain)

Alberto

Dear colleagues,

If it can help, please refer to our new article where we collected several references about this topic:

Fluoride is known to increase the incidence of bone fracture. Older adults have a 5- to 8-fold increased risk for all-cause mortality during the

first 3 months after hip fracture. We can therefore safely say Fluoride causes excess deaths via this mechanism.

See this interesting article with references.

Dear Michael after reading your answer i did look up to the internet and started reaading bout flouride in water.

I am now able to get some insight about the big problem the humans are facing.

Lets hope that the council for water management will take up the issue in a more seroius manner.

It also has made a difference to my understnading of the disease patterns of autoimmunity.

Thank you for the insights.

If OR is less than 1.0 it means that analysed factor is protective to this disease and in contrast above that 1.0 is a risk factor.

Good luck !

Asthma is a complex disorder which has many genetic and environmental causes.

Numerous genomewide studies for screening gene polymorphisms in asthma have revealed some susceptibility loci; among them are regions 2q, 5q, 6p, 11q, 12q, and 13q.63 Several polymorphisms are associated with asthma risk in IL-10, RANTES, TGFB1, ADAM33, CCR5, TLR-10, IL-4, IL-13, IL-8, IL-18, TNF, TLR-4, VDR and others.

Ref: Zhang J, Pare PD, Sandford AJ. Recent advances in asthma genetics. Respir Res 2008; 9: 4.

You could do PCA anyway and see afterwards if there are specific features which closely belong to single PCs.

By the way: considering the big number of features you will have large redundancy and reduncdancy is likely to affect the filter for feature selection as well. I.e., apart from not knowing the number k to choose, i would not be sure if you can trust your list.

Greetings, Sebastian

Hi Chandan,

That sounds unusual, it may be related to immune system activation by HCV and chronicity of the infection. The references listed may have some more information if you could tell us what they are?

BW

Tom

I would suggest you assemble a large population of flow volume plots , then do multiple linear or spline regressions on age ht sex etc for certain curve parameters, eg peak flow, time to return to zero flow, point of inflexion. Then construct a "predicted curve" for a person of certain age/ht/ sex etc do a spline fit using these calculated parameters.

the examples of predicted curves you give are only idealised.

doi: http://dx.doi.org/10.14740/jocmr2382w

J Clin Med Res. 2016;8(2):105-110

Influence of Body Composition on Lung Function and Respiratory Muscle Strength in Children With Obesity Dirceu Costa Juniora, Fabiana S. Peixoto-Souzab, Poliane N. Araujob, Marcela C. Barbalho-Moulinc, Viviane C. Alvesb, Evelim L. F. D. Gomesb, Dirceu Costa

less than 60% predicted value with variability +/-  30%    (for both FEV and PIFR)

absolute volumes depend on body size (age/ht/sex)

.

In the US, any of the approved fellowship training programs for allergy, asthma and immunology should be able to help training the staffs who would like to learn the treatment with immunotherapy. If you are not the candidate of fellowship program, you may need to contact with program director to discuss your individual situation.

Shih-Wen Huang, MD

The House Dust Mite (HDM)-induced asthma model in the mouse can be used to assess the in vivo efficacy of anti-asthma drug. The model features many similarities to human allergic asthma, including the presence of eosinophilic lung inflammation, release of inflammatory mediators, and cytokines primarily associated with TH2-type inflammation. In addition, total and differential cell counts of inflammatory cells in the lung can be performed in the bronchoalveolar lavage fluid at various time points to observe in time course of inflammation and evaluate the effects of compounds. Many studies in the past appeared to focus on acute allergen challenge procedures. It is recognized, however, that asthma is a chronic inflammatory disease resulting from continued or intermittent allergen exposure, usually via inhalation. HDM would be an excellent  allergen to develop chronic allergen exposure models in mice to study human disease of asthma..

Shih-Wen Huang, MD

My pleasure. BJCP

Thank you Dr Lam. You are correct sir. But your young patient who cannot follow your command what you will do for them clinically to detect wheeze which is audible in stethoscope?

I'll send you three bottles  -- how's that?

I think it has a role 

now I am start working on the role of protein profile in patients with UIP

waiting the results

Dear ahmed

there are many factors that indicate to asthma induced by ovalbumin such as physiological factor ( through hematology) immuniological factor ( through cytokines) and histological factor, the following artical can help you

thank you for your question

beta agonists are used for 2 main reasons

inhaled for treatment of airway obstruction in asthma and COPD 

oral or intravenous as tocolytics, to decrease uterine contractions in preterm labours 

Dear Anju,

Try to google the topic with "fexofenadine in comparison to..." comparison between H1-blockers".

Have a look at the Asthma UK website- there are loads of useful resources that we give out to our patients in our Asthma clinic. Including the ACT score, asthma management plans for individual patients. Good starting point.

I think the question is a real one as most clinicians would be asked by the patients, especially during the allergy seasons. The gentlemen above both offered the reasonable answers.

My take are:

First, the active immunological reactions in the host that resulted in the release of whole host of mediators. Those interleukins or cytokines are known to cause fatigue, especially interferon, IL-1, IL-6 and TNF.

Second, the quality of sleep suffered. Patients might toss around whole night without getting proper rest. They could hardly got into the state of deep sleep that relieve most of fatigue.

Third, we could not rule out what the drugs, especially of anti-histamine or decongestant(s) that might disturb sleep as well as causing drowsiness while trying to stay awake.

SWH

this is very important question even for me also. i insert 1.5 mL of PBS in a mice for BALF and i get average protein concentrion is 0.2 to 0.8 mg/mL. since in real time the total volume of surfactant of lungs would be less then 100 uL (cant say exactly) and we collect 1 to 1.5 mL total wash. so i am too waiting for answer of this question

These measures are much less reproducible than FEV1 within individuals and also suffer from lack of  reliable "predicted" values for epidemiology. Hence their use has declined and FEV1 dominates.

I USED for 4 yrs old child

Several studies have been conducted on the association between asthma  and vitamin D levels.  Asthma is a multifactorial disorder of the airways and various genetic and environmental factors contribute to the disease pathogenesis. As far as vitamin D deficiency is concerned, studies have reported controversial outcomes. Dr. Stephanie Korn and colleagues were the first to correlate severity of asthma with vitamin D status. In this cross-sectional study conducted on 280 adult asthmatics and 40 healthy volunteers,  vitamin D levels were similar in asthmatics (25.6 ±11.8 ng/ml) and healthy subjects (26.2 ±16.8 ng/ml), (p = 0.778).  Vitamin D levels were the lowest in severe asthmatics (24.0 ± 11.8 ng/ml), p = 0.046 compared to intermittent, mild or moderate, controlled and uncontrolled group. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3648461/

Several studies correlate vitamin D levels with asthma severity and have published different outcomes. In another retrospective study conducted in Soudi Arabia on 194 children with asthma, no significant difference was found in good asthmatics (53.4 ± 24.2) and poorly controlled asthmatics (51.5 ± 25.3), p= 0.657. Vitamin D levels were reported to be lower in females (65.5%) than males (46.8), p= 0.019.

Chun-Tao Liu and colleagues have conducted a meta-analysis on supplementation of vitamin D alongwith asthma controllers and effect on clinical outcomes in patients with asthma. In this metaanalysis, 903 patients with asthma were included and 453 received vitamin D supplementation alongwith common asthma controllers. It was found that vitamin D supplementation could significantly increase serum 25-hydroxyvitamin D levels (z = 5.50, P < 0.001 and z = 6.16, P < 0.001), but there was no effect of vitamin D levels on asthma exacerbation, FeNO, lung function (FEV1%) and asthma symptoms (ACT).

Thus, to find out if there is any link between poorly controlled asthma and vitamin D, more clinical trial need to be conducted and the factors involved and the mechanisms of pathogenesis should be explored to understand the exact scenario.

Increases in exhaled nitric oxide (FeNO), when measured daily, has been shown to predict moderate asthma exacerbations, as shown by van det Valk et al.

It is assumed that beta-1-antagonists have less effect on the pulmonary system. This is an experimental research  claim. Nonetheless,in real life and humans all 'beta1-selective' beta-blockers affect the pulmonary system. This is especially true in asthma, because it is an inherent characteristic of this disease that beta-receptors are different from those of patients with normal pulmonary function. In asthma the 'selectivity' is partially lost. However, it is uncommon that the effect is large and really clinically significant.

It is a common experience that patients with asthma and overlap syndrome are treated with inhaled beta-agonists and also receive oral beta-blockers. This is a pharmacologic  wrong choice.

In Morocco, you can contact 

Animal models are suboptimal for checking drug-interactions with regard to relevance in vivo in human (if this is your major interest). 

Sharing similar CYPs is normally not a problem when combining two drugs as long as effective concentrations are below saturating concentrations. Therapeutic concentrations are normally in the nmolar range. When combining two drugs that are both metabolized by the same enzyme, the enzyme is more active under combination. If one drug is an inhibitor and the other a substrate the interaction effect depends on the affinities of the compounds and the concentrations that are used. It would be helpful if you have information on Ki and Km on the compounds. Then you may suggest if there will be an interaction.

Best regards

Christoph 

The allergic specific immunotherapy is most effective treatment for IgE mediated diseases.It change the naturale course of disease.I work 16 years with SCIT andSLITH and I have very good resiltes.You can finfd it in my papers,

In my opinion eosinophil is a barrier breaker (independently to the fact if the effect is addressed to infectious/parasitic organism or to mucosal barrier like the bronchial one). Therefore, it develops hyperreactivity due to epithelial damage/denudation and local nerve irritation. In addition, the survival effect due to nerve growth factor (NGF) is insufficient because of low expression of respective receptors tyrosine kinase A (TrkA) in epithelial cells in bronchi. You can see the address: the www.novapublishers.com/catalog/product_info.php?products_id=31360&osCsid=dd67b6261b0c086c85e8f2108701869f

(Mingomataj et al. The magic eosinophil: a breaker of biological barriers. In: Eosinophils: Structure, Biological Properties and Role in Disease. Ed: Walsh GM. Novapublishers Inc.  2012, ISBN: 978-1-61122-270-8).

Dear Josh,

A double-blind, randomized crossover study in 28 asthmatic patients assessed the relative therapeutic index for inhaled formoterol and salbutamol. Pre-drug administration FEV1 (mean 2.08 l) was 49–93% of predicted and reversibility 16–82% after inhalation of salbutamol. Patients inhaled single doses of formoterol (Oxis®) (4.5, 18 and 54 μg, delivered doses) via Turbuhaler, salbutamol (Ventolin>®) (200 and 1800 μg) via pressurized metered dose inhaler (pMDI) and placebo at intervals of 48 h or more. Individual maximum FEV1 and minimum S-K+ were calculated. Relative local (maximum FEV1) and systemic (minimum S-K+) dose potencies, and their ratio, the relative therapeutic index, were estimated using a non-linear mixed effect model. The drug effects were well tolerated and dose dependent. A log-linear approximation was used to describe the bronchodilatory effect, whereas a sigmoid approximation was more apt to describe the decrease in serum potassium concentration. A bivariate dose–response model based on these principles was fitted simultaneously to all data. The mean relative therapeutic index between formoterol 4.5–54 μg given via Turbuhaler and salbutamol 200–1800 μg given via pMDI was estimated to be 2.5 in favour of formoterol; this trend was not statistically significant.

To view the full publication, please use the following link:

Eur J Clin Pharmacol. 2002 Jul;58(4):S61-7.

Assessment of a relative therapeutic index between inhaled formoterol and salbuterol in asthma patients.

Rosenborg J1, Larsson P, Rott Z, Böcskei C, Poczi M, Juhász G.

Author information

 

Abstract

To quantify the relation between local and systemic magnitudes of effects of inhaled formoterol and salbutamol.

Twenty-eight stable asthmatic patients completed this double-blind, randomised crossover study. Pre-drug administration FEV1 (mean 2.08 L) was 49-93% of predicted and reversibility 16-82% after inhalation of salbutanmol. Patients inhaled three single doses of formoterol fumarate dihydrate (Oxis) (delivered doses of 4.5, 18 and 54 microg) via Turbuhaler, two single doses of salbutamol (200 and 1800 microg) via a pressurised metered dose inhaler (pMDI) and placebo at intervals of 48 h or more. Individual maximum FEV1 and minimum S-K+ were calculated. A classic sigmoid model of log-dose response was used to discriminate pharmacologically between formoterol and salbutamol. Relative local (maximum FEV1) and systemic (minimum S-KC) dose potencies, and their ratio, the relative therapeutic index, were estimated using an on-linear mixed effect model.

The drug effects were well tolerated and dose dependent The bronchodilating effect was on a part of the dose response curve that could be well approximated by a log-linear function, the serum potassium suppressing effect sometimes was not (the lowest doses differed only marginally from placebo). Thus, a log-linear approximation was used to describe bronchodilation, whereas a sigmoid approximation was more apt to describe the decrease in serum potassium concentration. A bivariate dose-response model based on these principles was fitted simultaneously to all data. The mean relative therapeutic index was estimated to be 2.5 (95%confidence interval: 0.9-6.5).

The mean relative therapeutic index between formoterol (Oxis) 4.5-54 microg given via Turbuhaler and salbutamol 200-1800 microg given via pMDI was estimated to 2.5 in favour of formoterol; this trend was not statistically significant.

Hoping this will be helpful,

Rafik

these cells are the size of lymphocytes with very dense nuclei, I think  they could be apoptotic cells, perhaps due to therapy?

you can try confirm apoptotic cells by immunocytochemical detection of c-caspase 3?

check this article http://www.thelancet.com/journals/lanres/article/PIIS2213-2600(14)70050-5/fulltext?rss=yes , where similar cells are shown

If the crisis is moderate-severe you can't go around systemic CS, so use them but add shorts of rapid acting insulin according to glucose levels. Here a co-management with endocrinologist might be recommendable. concluding: asthmatic crisis in DM patient should be managed as any crisis, but adding rapid acting insulin according to needs (which can also be elevated due to infection ) 

Dear Collegeau!

What do you mean on"systemic side effect". I think one thing is the cortisol suppression and other things are the Cushing-syndrome, the osteoporosis or diabetes.  Sorry:The article is in Hungarian language, but you can use the references. Best regards

I think you may benifit from this:

Guideline on the Requirements for clinical documentation for Orally Inhaled products (OIP) Including the Requirements for demonstration of therapeutic equivalence between two inhaled products for use in the treatment of ASTHMA and Chronic Obstructive Pulmonary disease (COPD) in Adults and For use in the treatment of Asthma in children and adolescents  CPMP/EWP/4151/00Rev1, 22 January 2009 European Commission, Brussels, ENTR/CT 3, Detailed guidance on the collection, verification and presentation of adverse reaction reports arising from clinical trials on medicinal products for human use, Revision 2, April 2006

ot this :

Guideline On The Investigation Of Bioequivalence. Committee For Medicinal Products For Human Use (Chmp), European Medicines Agency (ema), Doc. Ref.: CPMP/EWP/QWP/1401/98 Rev. 1/ Corr, London, 20 January 2010.

            Available at: http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2010/01/WC500070039.pdf

I suggestion use the Beck anxiety and depression but you should consider other factors characteristic of their population