Cold or sinus infection?

[PatriceH]

I'm bummed...two days away from another herceptin treatment and I come down with a sore throat, cold or sinus infection?! Doc says to cancel if I have a fever (to protect the others in the chemo room) but otherwise come one down.

It's almost ironic that I get "sick" just as I'm nearing the end of treatments (August). All last year, everything went like clockwork....

I just HAVE to get well...I have to visit a friend's chemo graduation on Tuesday!

(just venting, I guess -- off to bed with tons of hot tea!)

[Ellie F]

Hi
Just wanted to offer a little sympathy that you are not feeling well. Also wanted to add that all through chemo I never had a cold, sore throat etc. Now since just on vit H since July last year I have had three!
best
Ellie

[Lani]

I have previously posted (3 times or more) about a woman who had a cough while on herceptin which disappeared when she was off it. She agreed to be biopsied (airways) not just while she was on it, but when she was off it to see if they could discover why. It turned out that while on herceptin she made hardly any of the "hair cells" which line the upper nose and filter out incoming "germs" and had about 70% less speciialized cells in her upper airways m such as Goblet cells, which help fight infection.

This is why I like for people to add their symptoms to the thread, now under Herceptin/tykerb, where they are invited to add their herceptin"side=effects" real or perceived. It is not always easy to know if symptoms are due to longer term side-effects of chemo and radiation therapy eg. to the immune system vs. side effects from herceptin. By adding your input, perhaps some researcher/oncologist/drug company person will try to figure all this out. And special thanks to the lady who let them biopsy her airways a second time, even though she was better (happend in Europe as I remember, as no US insurance company would have helped of course! and liability for an unneeded procodure even if she waived her rights would probably still be problematic)

I have also read that it is likely the same thing may hold in a different way for the GI tract ie, that less specialized cells may be made and take longer to replace.

Will try to put the search function on and repost it!

[Lani]

12-05-2007, 06:44 PM #4
Lani
Senior Member

Join Date: Mar 2006
Posts: 1,946
from an old post of mine
For those complaining of nasal/sinus symptoms/coughing which they relate to Herceptin, I submit the following two articles. The nose, like the more distant airways/bronchiols have ciliated epithelial cells (lining cells with tiny hairs which help trap bacteria, molds and other particulates) . These articles raise questions which may help explain symptoms while on Herceptin--showing that her2 is necessary not just in embryogenesis, but also in adulthood for repair of these kinds of cells. They may help explain your nasal complaints, the reports of rare pulmonary problems in patients on Herceptin and perhaps the dry-eye problem I posted on before. The more they look into what her2 does, the more they find!:


Am J Physiol Lung Cell Mol Physiol. 2006 Feb 17; [Epub ahead of print]
Related Articles, Links
*
Differentiation of Human Airway Epithelia Is Dependent on ErbB2.

Vermeer PD, Panko L, Karp P, Lee JH, Zabner J.

Internal Medicine, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA, USA.

A clinical case documented a reversible change in airway epithelial differentiation that coincided with the initiation and discontinuation of trastuzumab, an anti-erbB2 antibody. This prompted the investigation into whether blocking the erbB2 receptor alters differentiation of the airway epithelium. If so, blocking or exogenously stimulating the receptor would lead to consequences on differentiation. To test this hypothesis, an in vitro model of well-differentiated human airway epithelia was treated with trastuzumab or heregulin-alpha, an erbB ligand. In addition, co-culturing with human lung fibroblasts tested whether in vivo subepithelial fibroblasts function as an endogenous source of ligands able to activate erbB receptors expressed by the overlying epithelial cells. Epithelia were stained with hematoxylin and eosin and used for morphometric analysis. Trastuzumab treatment decreased the ciliated cell number by 49% and increased the metaplastic, flat cell number by 640%. Heregulin-alpha treatment increased epithelial height, decreased the number of metaplastic and non-ciliated columnar cells while it increased the goblet cell number. We found that normal human lung fibroblasts express transforming growth factor-alpha, heparin binding-epidermal-like growth factor, epiregulin, heregulin-alpha, and amphiregulin, all of which are erbB ligands. Co-cultures of airway epithelia with primary fibroblasts increased epithelial height comparable to that achieved following heregulin-alpha treatment. These data show that erbB2 stimulation is required for maintaining epithelial differentiation. Furthermore, the mesenchyme underlying the airway epithelium secretes a variety of erbB ligands that might direct various pathways of epithelial differentiation.

PMID: 16489114 [PubMed - as supplied by publisher]


1: FASEB J. 2005 Aug;19(10):1374-6. Epub 2005 May 27.
Related Articles, Links
*
ErbB2 activity is required for airway epithelial repair following neutrophil elastase exposure.

Fischer BM, Cuellar JG, Byrd AS, Rice AB, Bonner JC, Martin LD, Voynow JA.

Department of Pediatrics, Duke University Medical Center, Durham, North Carolina 27710, USA.

In cystic fibrosis and chronic bronchitis, airways are chronically injured by exposure to neutrophil elastase (NE). We sought to identify factors required for epithelial repair following NE exposure. Normal human bronchial epithelial cells were treated with NE (50 nM, 22 h) or control vehicle. Following NE treatment, we found a marked and sustained decrease in epithelial proliferation as detected by Ki67 immunostaining. 3H-thymidine incorporation was also initially depressed but increased over 72 h in NE-treated cells, which suggests that DNA synthesis constitutes an early repair process following NE exposure. We hypothesized that ErbB2 receptor tyrosine kinase, a regulator of cancer cell proliferation, was required for epithelial DNA synthesis following NE exposure. Immediately following NE treatment, by flow cytometry analysis, we found a decrease in ErbB2 surface expression. Protein levels of the full-length 185 kD ErbB2 receptor significantly decreased following NE treatment and smaller ErbB2-positive bands, ranging in size from 23 to 40 kD, appeared, which suggests that NE caused ErbB2 degradation. By real-time RT-PCR analysis, we found no change in ErbB2 mRNA expression following NE treatment, which suggests that changes in ErbB2 protein levels were regulated at the post-translational level. Following NE treatment, full-length 185 kD ErbB2 levels increased to pretreatment levels, correlating with the increase in thymidine incorporation during the same time period. Importantly, inhibition of ErbB2 activity with AG825 (5 microM) or Herceptin (3.1 microM), an ErbB2-neutralizing antibody, blocked thymidine incorporation only in NE-treated cells. These results suggest ErbB2 is a critical factor for epithelial recovery following NE exposure.

PMID: 15923396 [PubMed - in process]



I started the post with my summary:
"For those complaining of nasal/sinus symptoms which they relate to Herceptin, the following two articles may hold clues as to what may be going on. The nose/airways have ciliated epithelial cells (lining cells with tiny hairs which help trap bacteria, molds and other particulates) and other specialized cells (including further down the "airways" in the bronchi and bronchioles). These articles raise questions which may help explain symptoms while on Herceptin--showing that her2 is necessary not just in embryogenesis, but also in adulthood for repair of these kinds of cells. They may help explain your nasal complaints, the reports of rare pulmonary problems in patients on Herceptin and perhaps the dry-eye problem I posted on before. The more they look into what her2 does, the more they find!:"

A “translation” of the “Greek” of the two articles:

Because of a case of a patient whose airways changed when Herceptin treatment was started and when Herceptin was stopped in terms of which types of specialized cells were present/absent they tried in a petri dish to see what happens to airway cells and found:

Trastuzumab treatment decreased the ciliated cell number by 49% and increased the metaplastic, flat cell number by 640%.

Thus the cells necessary to fight infection were more than halved and the cells with little specialized function, which do not secrete or trap bacteria, mold or particles went up by more than 6 fold.

In the other article, after bronchitis or other diseases where a white blood cell enzyme injures airway (bronchial) lining tissue her2 is necessary to repair the damage caused by this enzyme in an adult. The "Greek" is just describing how they proved the mechanism of how this occurs, at what step it occurs and whether the changes were on a gene or protein level.

Both articles emphasize that her2 fulfills physiologic functions in an adult and Herceptin can potentially adversely affect those functions. Epithelial cells are numberous throught the body--thhey line organs facing the "outside world"(which is sometimes inside as in the stomach and intestines) they function to keep infectious and dangerous particles out, secrete substances to lubricate and or digest, etc. Her2 seems to be necessary to keep these cells specializiing to serve different necessary functions and to repair/replace damaged cells.

Thus it seems it is not just the heart that Herceptin affects

[Lani]

PS There is something called "post-marketing research" that drug companies are required to carry out once they get FDA approval for their drug. As far as I can see there don't seem to be a lot of penalties carried out if it is not vigorously pursued. This requirement is in place so that, as the drug is used in many more people than received it during the clinical trials, they become aware of problems they didn't see in the larger study, especially if it is found in subgroups of patients not widely represented in the trials.

It took EONs before they found out black people did not respond to antihypertensive drugs the same as non-black people.

This part of the FDA requirement depends on doctors to let the drug companies or FDA know and for the drug companies to compile the figures and make them known.

Do any of your doctors send your complaints on?

I am asking this rather naively, as I really don't know how this works in reality. That was the reason I started that now long thread. Please remember to add to it--it might prove usefull for someone WHO IS LOOKING
someday.

THanks

[Hopeful]

Lani,

Do those same small hair cells that grow in the nose and intestines grow in the ears? I am curious, because my main Herceptin SE (which continues 3 years after I completed Herceptin tx) is tinnitus.

What do you think?

Hopeful

[Lani]

I may have been unclear--the hair cells in the nose are affected as are other specialized cells such as Goblet cells in the airways. It may be that specialized cells in the GI tract are affected but these are not "hair cells" and may or may not have anything to do with infections within the GI tract.

I remember finding out herceptin affected the cells in the lacrimal gland (tear forming cells) but have not so far seen anything about cells in the ear (but now I will look).

This is just an illustration of my point. The PDR (reference book about drugs) and the info sheet packed with every drug is supposed to have complications listed even if they occur only in about 1 in 100,000 patients I had heard. Once the drug is taken widely they need to gather that info so it can be put on the labels and in the PDR (Physicinans' Desk Reference) How can they do that if the oncologists and drug companies are not actively asking about side effects, writing them down, sending them on and tabulating them?

I don't think they truly understand the causes of tinnitus, but it is associated with certain drugs, like aspiring. Have you tried to check out if it is listed as a DELAYED side effect after any of the chemotherapies you received?

I will try to check out if it has been described with herceptin.

[Lani]

http://her2support.org/vbulletin/showthread.php?t=40385

[Hopeful]

Have you tried to check out if it is listed as a DELAYED side effect after any of the chemotherapies you received?

Lani,

I did not receive ANY chemotherapies, so it is not a delayed side effect of that. It came on abruptly after my third tri-weekly Herceptin tx. I had attributed it to the AI (Femara), as it was when I hit the six week mark of taking that drug, and I think had just reached a "steady-state" blood level of it. I did report it to the manufacturer of Femara, and they said they would add the SE to their list of after-market SE's. This has been frustrating, because, as is often the case when you take drugs in combination, it is difficult to sort out which SE goes with which drug. I would be interested in anything you find out about Herceptin and tinnitus.

Thanks,

Hopeful

[Hopeful]

I had read that thread on tinnitus before; I started my own back in 2006. The people who posted on Rich's thread talked about pounding sounds. I do not have that - what I hear is a very high pitched screech or whistle, almost like background noise you get when you have poor reception on the radio or tv. It is in both ears.

Hopeful

[Lani]

No luck so far putting tinnitus and herceptin into pubmed and google (but I bet you have done that as your posts show you to be a "searcher" not afraid to go hunting for information.

Will continue to keep my eyes open, but I would suggest adding this to the infamous herceptin side effect thread so others can chime in and perhaps someday someone will get interested into looking into these things. By the way, did you get carboplatin as platinum based chemos are known to be ototoxic.

Are you on any meds now?

[Hopeful]

By the way, did you get carboplatin as platinum based chemos are known to be ototoxic.

Lani,

As I stated above, I HAVE NEVER HAD CHEMOTHERAPY OF ANY KIND. It was recommended and I declined it, and my onc offered me a year of Herceptin monotherapy, which I accepted. I took an alternating course of Femara and Arimidex, trying to combat the tinnitus, arthralgia and atrophic vaginitis symptoms, for three years. I stopped the AI's on September 30, 2009 and am not currently on any medications.

Thanks for your help!

Hopeful

[Nancy L]

I am convinced that none of our side effects are passed on to the right people. Case in point----all of the women I have met in cyberspace who have experienced permanent hair loss from receiving Taxotere. All the docs have said to us is "that is not suppose to happen". I would be willing to bet money that nobody on this site was ever told before receiving Taxotere that this happens in a small percentage of cases.

Lani, I find your posts so interesting. Thank you. The information about Her2 in this post helps explain a lot about my respiratory issues.

[schoolteacher]

Thanks, Lani. I have had three respiratory infections this spring. I have been on Herceptin over two years. Maybe this is why I have had them.

Amelia