Search This Blog

Monday, July 11, 2016

Current concepts in chronic inflammatory diseases: Interactions between microbes, cellular metabolism, and inflammation

You are more than just one human being.  That may sound like an inspirational quote, but it’s actually a scientific fact: there are literally millions of bacteria living on, in, and around you that play crucial roles in the ways that your body and your mind work.  And now, thanks to newer technology, we have the ability to see how these ‘old friends’ – bacteria have likely been around since the emergence of humans – interact with our own cells to change how our immune system works.
In this month’s issue of the Journal of Allergy and Clinical Immunology, Garn and colleagues provide an overview of how these microbes influence our metabolism and can lead to inflammation, based on the insights from the International von-Behring-Röntgen-Symposium (J Allergy Clin Immunol 2016; 138(1): 47-56).  While our knowledge of the microbiome keeps on growing, the fact is that there remains so much to be researched.  For example, how does our modern age of hygiene, where we have eliminated so many of the old infectious agents with which we have co-evolved, impact chronic inflammation?  How do resident microbes interact with food to cause inflammation, or resolve it?  What role does biodiversity (which plummets while on antibiotics) play in maintaining the balance between promotion and resolution of inflammation?  And how do these microbes educate our immune systems during infancy and childhood?  Unfortunately, these questions remain mostly unanswered but there are some promising leads.  For example, a study involving 560 babies of families from Baltimore, New York City, and St. Louis demonstrated that exposure to allergens in the first few months of life may be associated with a reduced risk of recurrent wheeze, while exposure to microbes may reduce both the risk of atopy and atopy plus wheeze.

Extracellular RNA, DNA, and proteins that may come from microbes have been shown to mediate inflammation.  These molecules alter the cytokines released by our own cells, and can lead to upregulation of inflammatory responses.  While research is extremely preliminary, the influence of the microbiome on allergic, autoimmune, gastrointestinal, and neuropsychiatric disease is becoming more and more appreciated, possibly opening doors to new management strategies.  So embrace your inner germs and realize that you’re more than just one, sole human being.

Friday, July 8, 2016

Inflammatory mechanisms in patients with chronic obstructive pulmonary disease

C-O-P-D (chronic obstructive pulmonary disease) is a series of four letters that strikes terror in the hearts (and lungs) of millions throughout the world.  It’s a condition in which there is chronic inflammation within the lungs that leads to their destruction, causing problems in breathing.While the consequences of COPD have been long known, the immunology behind it is still largely unknown.  In this month’s issue of the Journal of Allergy and Clinical Immunology, Dr. Barnes reviews the inflammatory mechanisms behind COPD (J Allergy Clin Immunol 2016; 138(1): 16-27).
As he mentions, one of the difficulties behind figuring out how immune dysfunction causes COPD is that COPD doesn’t seem to be a single disease.  Different types of immune cells and mediators seem to be involved in different ways in different patients, and our knowledge continues to grow about how we can tease apart all these endotypes and phenotypes.

However, some common themes are emerging.  Patients with COPD have lower levels of anti-oxidants, leading to excess reactive oxygen species (ROS), which, in turn, trigger the inflammatory response.   These ROS may also promote lung cancer by activating growth factors and damaging DNA directly.  The other major common theme is that there is systemic inflammation that “spills over” to cause an increased risk of heart disease, diabetes, lung cancer, and pneumonia.

Currently, we don’t have treatments to help reverse the damage from COPD, and most of our efforts remain in prevention and control of symptoms.  But with greater knowledge on the roles immune system, we may be able to help people, who have been diagnosed with COPD to regain control of their lungs, and their lives.

Thursday, July 7, 2016

Intranasal triamcinolone use during pregnancy and the risk of adverse pregnancy outcomes

It’s not surprising that expecting mothers carry a lot of weight in their bellies.  But they also carry a lot of weight on their shoulders.  What to do, and what not to do, complicates nearly every decision when there’s a second person to think about, even the relatively minor act of using a nasal steroid spray to treat allergic rhinitis.  Fortunately for them, Dr. Berard and colleagues conducted a study to help address these concerns (J Allergy Clin Immunol 2016; 138(1): 97-104).
They looked at nearly 300,000 pregnancies in Montreal between 1998 and 2008 to find pregnant women who took intranasal triamcinolone as well as other intranasal steroids.  They then looked at the number of major abnormalities at birth, spontaneous loss of pregnancies, and underweight newborns, and compared the rates to those who did not use intranasal triamcinolone. 
For the most part, the results are comforting.  They suggest that there is no link between using intranasal triamcinolone (and, by extension, all nasal steroid sprays) and major birth abnormalities or spontaneous fetal loss.  However, out of 296 pregnancies, there were 5 cases of respiratory defects in babies born to mothers who used triamcinolone during the first trimester.  This was a statistically significant finding.  Of note, no link between respiratory defects and other nasal steroid sprays could be found.
The implications of this study are also covered in an accompanying editorial by Drs. Namazy and Schatz, who praise the importance of the study, the first of its kind trying to determine the safety of nasal steroids during pregnancy (J Allergy Clin Immunol 2016; 138(1): 105-106).  They also mention that controlling allergic rhinitis during pregnancy may be helpful in preventing snoring, which is linked to hypertension during pregnancy.Namazy and Schatz try to make sense of why triamcinolone may be correlated with respiratory defects.  It may be due to unmeasured confounders, but that is unlikely since these confounders were present in both the triamcinolone and non-exposed groups.  Or perhaps it’s a biologic effect of triamcinolone, since animal studies of intramuscular triamcinolone have shown similar defects.  Or, it may just be due to pure chance.

Regardless, the authors suggest that, to be on safe side, intranasal steroids like fluticasone or mometasone should be used instead of triamcinolone during the first trimester.