Lung Diseases - Science topic

see attached refs

Bronchoalveolar Lavage of Murine Lungs to Analyze Inflammatory Cell Infiltration - PMC

A simplified method for bronchoalveolar lavage in mice by orotracheal intubation avoiding tracheotomy | BioTechniques

Hi Deepdarshan Urs

Have you done characterization of the organic dust? For VOC's, PAH'S or metals?

I expose C67/BL6 mice with PM 2.5 and the functional parameters of the mice lungs are affected from 15th day itself. So if you have instruments to assess the lung function such as whole body plethysmography or FlexiVent analysis, you could check the same at 15th day interval and from then on every 7 days interval to check how the inflammation and lung function are being affected due to repeated exposure of organic dust particles.

Thanks

Samir

Yes, one of the manifestation of the disease involves lungs. and long term complication also involves changes in lungs. it is definitely a pulmonary disease. though it involves other organs also, extent of pathologies of other organs are yet to completely documented.

Thank you so much Wojciech Feleszko and Jigneshkumar Parmar

I cannot help. I deal only with skin and local pain without AINS treatment

JEAN

ou can find some CT examples with nodules and normal occurences

I think that women are more than men for exposure to COPD.

The main alternatives energy sources to the use of fossil fuels for electricity generation are:

a) Renewables;

b) Nuclear energy.

However, not all countries are ready to replace the use of fossil fuels for electricity generation with the use of renewables and nuclear energy altogether. Renewable energy sources are unstable, such as solar and wind power; both types of renewables depend on climate conditions. Some others are not available in the country such as geothermal or their presence is not strong enough to represent a real alternative to the use of fossil fuels for electricity generation such as hydropower.

The use of nuclear energy for electricity generation is not a cheap option, and many countries have not adequate infrastructure and the qualified workforce to use this type of energy source for electricity generation.

For this reason, a country should study all types of energy sources available in the country very carefully and select the most economical and clean combination of energy sources to build its energy matrix.

In continuation: I do like PAV+ (similar capability in othe ICU vents), dfor patients that can control thier ABG needs. It provides very useful in formation on compliance, resistance, intrinsic PEEP diaphragmatic loading etc. However, once you have this data the bedside clinican needs to synthesiize the best short term support and long term weaning plan for this patients evolving pulmonary support needs. THis includes anticipating mitigating and reacting to the evolving pathologies and responces to treatments. This becomes all inclusive in the analysis and potential postive patient outcome while the antithesis also is true.

Hi Ramon Martinez

Thank you very very much Sir, this link worked.

I was unable to download the annual data from WHO's data bank.

Thank you again.

mostly alveolar macrophages.. Alveolar epithelium. Lymphocytes. In addition to another cells according to the pathology

Prevention is better than cure and here the role of Environmental Scientists/managers to prevent the health hazards by introducing the appropriate technologies for cleanup. By this way Anaerobic digestion is helpful for decontaminating the environment and breaking the chain of disease. Conclusively it will help to minimize the risk of disease. I am also curious about to know if any other direct linkage in between.

Thanks and regards

Dr Shankhwar

Maybe L132 and MRC-5....

The attached refs give more details.

It may it is highly diffusible and if the patient survives long enough. The patient may suffocate due to poor lung function from chronic lung infection and worse lung function by lower expiratory volume. It may only be possible in acute infection because biofilm infection may not produce as much as 100uM needed for the blue tinge of the sputum. 

You can digest tissue in RPMI-1640 (2-3% serum) containing 0.8mg/ml Dispase and 0.2mg/ml Collagenase P (Roche). Tubes should be incubated at 37˚C in a water bath or incubator and gently invert at 5-10 min intervals to ensure the

contents are well-mixed. After 30 min,gently collect the cells in another tube and add the fresh media with collagenase and dispase. Total process will take around 60 min. Centrifuge the cells and plate them in fresh media.

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

LC-MS

Hi

Great case.

It all depends on the resources you have. On the second image you show us, it looks like there is an airway adjacent to the mass. I would probably attempt EBUS with TBNA and have rapid on-site pathological evaluation, if available.

If surgery is more readily available than bronchoscopy, I would do PET/CT scan followed by surgery if FGD avidity is high. 

It doesn't look like VATS would be of high yield here. 

Hope it helps!

Keep us posted about the results.

The AAP is not recommending steroid use to prevent BPD. The general agreement is late use of steroid may help to extubate premature infants on ventilator. You can look into DART protocol and some of my colleagues are very into using low dose hydrocortisone for that purpose.

In the Netherlands we have widely implemented the term Lung Attack about 3 years ago (in a campaign from the Dutch Lung Foundation) and has landed quite well (until then there was not an widely accepted alternative to the complex term 'exacerbation'). It somehow emphasizes the severity of these events in terms of it's impact on mortality (which is worse compared to cardiac failure/hear attack), accelerated lung function decline and quality of life. Another advantage is that it underlines the acuteness of these events. 

Dear Collegue

I have colleague ... Dr  Rina Triasih Indonesian Pediatricians from Universitas Gadjah Mada .. PhD graduate from Melbourne University and published many international publication. If you need more information about her I will give you further contact information

Best wishes

Awalia Febriana 

Hello,

Additionally the following might help you:

Regards,

Parul

As CF is caused by a mutation in the CFTR I don't see a role for LT in the disease.  My thoughts would be that because of the insussipation of mucus agents to help clear and thin the mucus plus a bronchodilator would be about the best course to help with the cough.  Remember that as the LIR become activated by the eventual narrowing and mucus accumulation they will add to the cough.  Using a beta agonist to open the airways as much as possible under these conditions will help to reduce the LIR activation and there fore the cough.  Frustrating as it is, I don't see that a LT antagonist would help.  If you were to try one (singular presumably) you may be served by looking for LT metabolites in urine first to assure that there is in fact a LT component to what you are trying to treat. 

Yes, trans-dermal! years ago, dermatologist Dr Don Rosenthal and I published a case report in which a 30+ year old farmers wife had mixed a herbicide (Paraquat) to spray their fruit trees. She did not take the advised precautions to wear a total covering. She had a scratch on her forearm prior to mixing the Paraquat which subsequently became necrotic and she simultaneously, over about 2-3 weeks developed respiratory failure due to a rapidly developing neutrophilic inflammatory response and ARDS from which she died in about 3 weeks. Since her husband did the spraying her only exposure was dermal!

ILD with preserved or increased lung volumes 

lymphangioleiomyomatosis,

pulmonary Langerhans cell histiocytosis

some sarcoid patients

concomitant emphysema or asthma.if ILD develops in a patient with significant emphysema,

combined pulmonary fibrosis emphysema symdrome

No

I need to strongly second the statements of Jean-Martin as regards this and emphasize that unless you do histopathological analysis of at least some of your gross lesions your results will be dubious at best. With proper experimental planning and knowledge of the disease distribution in the lung lobes (particularly possible in the case of widely disseminated or multifocal patterns) you can designate a lung lobe consistently for pathology.  You then tie it off and formalin fix it separately. This leaves the other lobes for use in other analyses. This is done regularly for ferrets and even mice so certainly might be done for rabbits.  Then you can do gross/histo correlates for every animal in your study. 

De acuerdo con los compañeros anteriores.

Pero hay que conocer la practica de la percusion.

No para pacientes obesos o con gran enfisema subcutaneo.La auscultacion sin fonendoscopio utilizando el oido puede ser util ante un accidente en carretera o incluso en puertas de urgencias de un Hospital.A veces no hay tiempo para llevar el paciente  a diagnostico por la imagen.El neumotorax hipertensivo requiere una rapida actuacion.Sobre todo si hay que intubar al paciente que agravara la hipertension.

Recordar que con una radiografia en bipedestacion al acostar al enfermo ,la patologia pleural cambia.Yo siempre practico la percusion en estos casos.

READ ABOUT THE UREA METHOD...

Sounds like a good first approximation would be to look at the literature on lung function of people smoking cigarettes. I might suspect that incense might be more like second-hand smoke exposure, so the effect will be less than for someone who is smoking. I would therefore try and increase my sample size.

Search the internet for sample size calculators, and you can find many. They generally assume your sample is from a population that is normally distributed. They also require information that you don't have -- though you could use smoking studies here too.

Talk to a graduate student or instructor in the Statistics department. They should be able to help you avoid some of the more common problems. How you define your population, and how you sample that population can cause as many problems as having too few samples.

Do fully agree. In itself ILD as a side effect of cyclophosphamide is very rare. So, do exclude other causes that may be related to the development of ILD in this patient. Might it be related to the underlying disease for which you gave the cyclo; and, of course do exclude (opportunistic; PJP) infection.

i think this study will help

Dear Dr. Wrobel,

To my Experince, it is a Contraindication, I do not recommend because of the increased risk of Pneumonia. And it can be not tolerated for Gold-D COPD /Empysema patients.

Sputum Culture should be studied in all patients before the BLVR procedure.

Regards

Recruitment of volunteers may be very ethical but a control group thus formed may be quite inadequate in the framework of a particular study. I still believe that one should, first of all,  think about characteristics which must be equal in the groups to be compared.. As to the ethics, the first question is whether the new  knowlege you hope to obtain is worth invasive tests at all.

Thank you for your useful comments

Simple answer YES. See for instance:

Aerosol drug delivery: developments in device design and clinical use

Dolovic at al

The Lancet, Volume 377, Issue 9770, Pages 1032 - 1045, 19 March 2011 

Sometimes this type of drug application is not very effective due to large losses in the aerosol inhalation

MAC lung disease can be difficult to treat and can have difficult to tolerate side effects.  Having said this, most experts in this area do not start with injectable agents.  For MAC lung disease a typical regimen would include a macrolide, rifampin and a fluoroquinolone or ethambutol 3x per week (daily if severe or cavitary disease).  Injectable agents are generally reserved for severe cases that are resistant to oral therapy or have become complicated (extensive pleural disease for example).

The goal is to continue therapy for at least 12 months after the last negative sputum culture, and patients need to understand that prolonged therapy is essential.  In many patients, achieving a cure may not be realistic and it may be necessary to treat to achieve control rather than cure.  You will find the ATS guidelines for non tuberculous mycobacterial lung disease useful:

Dear Hassan,

Many thanks for this answer. Attached is a link to the paper which was eventually published. http://www.hcaf.biz/2014/Respiratory_CMV.pdf

Any thoughts welcome.

Cheers

Rod

Dear Priya, this patient has most likely "Pulmonary hypertension due to left heart disease" not "Pulmonary arterial hypertension". This differentiation is key, because treatment is completely different for these two types of PH. How high is mPAWP or LVEDP in your patient? How high is the gradient between diastolic PA pressure and mPAWP? In case of high mPAWP heart failure medication is recommended (optimisation of LV function). There is no robust data that supports the use of Sildenafil in such patients.

My approach is simple: if the pleural effusion is simple and can be easily drain I prefer  medical therapy + chest tube drainage. However, if effusion is complicated or loculated  I prefer VATS. I may consider DNAase/fibrinolytic over surgery if patient is on mechanical ventilator with moderate to high settings  or hemodynamically unstable. 

Dear Mike

Please a recent article that uses murine alveolar type I cell line.

J Gen Virol. 2014 Feb;95(Pt 2):350-62. doi: 10.1099/vir.0.058438-0. Epub 2013 Nov 16.

Characterization of innate responses to influenza virus infection in a novel lung type I epithelial cell model.

Rosenberger CM1, Podyminogin RL, Askovich PS, Navarro G, Kaiser SM, Sanders CJ, McClaren JL, Tam VC, Dash P, Noonan JG, Jones BG, Surman SL, Peschon JJ, Diercks AH, Hurwitz JL, Doherty PC, Thomas PG, Aderem A.

Author information

1Seattle Biomedical Research Institute, 307 Westlake Avenue North, Suite 500, Seattle, WA 98109, USA.

Abstract

Type I alveolar epithelial cells are a replicative niche for influenza in vivo, yet their response to infection is not fully understood. To better characterize their cellular responses, we have created an immortalized murine lung epithelial type I cell line (LET1). These cells support spreading influenza virus infection in the absence of exogenous protease and thus permit simultaneous analysis of viral replication dynamics and host cell responses. LET1 cells can be productively infected with human, swine and mouse-adapted strains of influenza virus and exhibit expression of an antiviral transcriptional programme and robust cytokine secretion. We characterized influenza virus replication dynamics and host responses of lung type I epithelial cells and identified the capacity of epithelial cell-derived type I IFN to regulate specific modules of antiviral effectors to establish an effective antiviral state. Together, our results indicate that the type I epithelial cell can play a major role in restricting influenza virus infection without contribution from the haematopoietic compartmen

Yes. All types of granuloma can be found in a single patient.

Sample size estimates are not trivial. One can easily use any number of statistical software packages (PASS, SAS, CreoStat, et al.), but these can be "dangerous" in the hands of a novice who does not understand the underlying assumptions/calculations. I would suggest either of 2 options: (1) contact a statistician to help, or (2) spend a few days going through the text by S C Chow et al (2008) "Sample size calculations in clinical research" Chapman and Hall. This book is very helpful both in explaining the process, but also has extremely useful tabulated results that might actually spare you from doing the calculation by hand or with software.

The original paper from Morris & Temple Preventive Medicine 1985 vol 14 pg 655- 662 compared different methods but the authors suggested that the formula based on FEV1 was superior.

Lung age = (2,87x height in inches) - (31,25 x observed FEV1) - 39,375

But Vito has a valid point….

Seyed es mi opinión.

En patología maligna pienso que no hacemos favor al paciente. Si la carcinomatosis es muy avanzada. Si no es muy avanzada indicaría la fenestración pericardica en la pericarditis constrictiva sin pleuritis constrictiva. Si la hay practicar drenaje anterior o contralateral.

En patología benigna en el paciente joven siempre cirugía. En el paciente adulto la pericardiectomía total o parcial si compromete la vida del paciente.

Siempre valorar en ambos casos individualizando al paciente.

Me alegro de conocerte.

Dear Marko you can download my full paper on my profile... If you have some comments, be free to send it...

What type of cells you want to identify?

a cytokeratin 19 antibody is a good marker for bronchial cells.

DClamp allows to visualize all type II pneumocytes.

Regarding the dendritic cells, there are several markers specific for each family of DC:

Langerin or ASGPR for the epithelial tissue.

DCsign or MR, for the alveolar tissue.

In our institutional experience, when the biopsy is done for a patient who is in an outpatient setting it usually provides useful information and a therapeutic change for over 50% of the patients. For critically ill and mechanically ventilated patients that require high PEEP and FiO2, perhaps it is too late and surgical intervention not only adds insult to injury but also doesnt change much in terms of therapy. Our mortality rate for outpatients is 0% and for ICU patients jumps to 45%.

Commonly used algorithms are using center line detection methods and reorientation along that center line in order to initialize segmentation algorithms, such as

E.Ukwatta et al. "Joint Segmentation of 3D Femoral Lumen and Outer Wall Surfaces from MR Images" MICCAI 2013. 534-541.

I've seen something nice at CVPR this year, that could work well too: Zhu et al. "Graph-Based Optimization with Tubularity Markov Tree for 3D Vessel Segmentation" CVPR 2013.

Other than that you can always apply a Frangi vesselness filter and threshold the probabilistic result with an easy matlab script. The filter can be found on Matlab central. Hope that helps! Good luck!

Thanks, Monika. Do you know if Cryomatrix is any different from e.g. formalin for this type of preservation? I reformulated the question to reflect the potential problem of not wanting to instil any fixative into the lungs. BR, Jitka

Dear Sheila

As a part of CPT we manage and treat not only the disease itself but its clinical consequences as well.

One of the consequences of pleural effusion is lung volume reduction which could couse ventilation-perfusion mismach, hypoxemia and increasd work of breathing.

It means that Pleural effusion by itself is not an absolute CI

But several PT interventions may be contraidicated in case of Pleural effusion.

Some possible interventions that can improve ventilation-perfusion ratio are positioning: side lying (abdomen free) with unaffected lung down, modalities to decrease stress and WOB (music, massage, , appropriated breathing pattern) , and maintain the general mobility.

You can find some suggestions for treatment in the following textbooks:

1. Physiotherapy in respiratory care (by Alex Hough)

2. Emergency physiotherapy (edited by Beverly Harden)

First, let me declare a potential conflict: our company Indoor Biotechnologies manufactures purified natural and recombinant allergens. However, since my days in academia (University of Virginia), we have long held the view that there are flaws in both OVA and HDM models of asthma. OVA is a relatively minor food allergen and has been used mainly because it is inexpensive and readily available. Use of OVA is fundamentally no different from using other model protein antigens, such as lysozyme. HDM models are a step up, but the problem here is that the HDM used by different groups is not standardized, and even if standardized HDM is used, there is often little evidence that the inflammatory responses generated are actually caused by mite allergens, rather than other antigens and biologics in HDM extract. If one follows the logic of using HDM, then egg extract should be used instead of OVA!

So my advice to Duc is to think carefully about the consequences of using either of these antigens. Models using HDM, need to evaluate antibody and cellular responses to the major allergens, e.g. Der p 1, Der p 2 and others, as well as consider the potential role of endotoxin, chitin and other potential adjuvants in HDM extracts, if they are to pinpoint the mechanisms of allergic inflammation and AHR.

No, the amount of emphysema is based on the attenuation of the xray beam as it passes through the lung. If the collimation gives slices more than 1 mm thick, then the number in Hounsfield units should be more than -950 HU, the standard amount for today's high resolution scans. If you are using, say, scans of 2.5 to 5 mm in thickness, for example, a cutoff of -910 to -920 HU would be better. As you can see, it is a little arbitrary! I think the commercial software, such as Vida, is set up for -950 HU.

Airway dimensions, thickness and lumen size, are tricky, since they depend on the size of the airway normally. The right way to do it, and the most tedious, is to make several observations and plot them in the form of percent of the airway wall area or the square root of the airway wall area (but not mixed up!) against the length of the internal perimeter of the airway where it was measured, making sure that the plotted values are spread out a bit. Of course, you calculate these measurements from your actual measurement of the diameter of the airway itself and its lumen. An arbitrary value of this perimeter (iP=10 mm) is what is usually reported, so it must lie on the plot as well. And that is the number that explains airway wall thickness. I have no idea what commercial software does here, since my experience is with a home-grown program. I am not familiar with the 0-6 method of grading, though it is as good as any.

A new idea is that of air trapping, as opposed to emphysema alone. Certainly emphysema causes air trapping, but many cases with significant airway problems have no emphysema, How this is to be measured is still under debate and study. For example, does an increase in small airway wall thickness account for air trapping? It usually requires an expiratory CT scan and careful observation of the lungs for irregular air trapping, or a mosaic pattern. Quantification is much debated.

Dear Araz,

the pulmonary endothelium is known to be the main source of circulating ACE in the body. Main work in this field has been scientifically done by Sergeij Danilov and his group. However most of his work is on ACE I.

some papers:

Heterogeneous distribution of angiotensin I-converting enzyme (CD143) in the human and rat vascular systems: vessel, organ and species specificity.

Metzger R, Franke FE, Bohle RM, Alhenc-Gelas F, Danilov SM.

Microvasc Res. 2011 Mar;81(2):206-15. doi: 10.1016/j.mvr.2010.12.003. Epub 2010 Dec 16.

There is a work in mice which says that ACE II was primarily epithelial in the lung however:

Angiotensin converting enzyme 2 is primarily epithelial and is developmentally regulated in the mouse lung.

Wiener RS, Cao YX, Hinds A, Ramirez MI, Williams MC.

J Cell Biochem. 2007 Aug 1;101(5):1278-91.

best wishes

Kai

One of the resources most used by US physicains can be found at the following link. It will go far to helping with an approach to your patients and which medications are effective:

Thanks a lot! This reference will really help to find the right product!!