Wheezing after respiratory virus infection...

Takeyama and colleagues from Japan delved into the viruses present among young children (= 3-years of age) hospitalized with a clinically defined lower respiratory tract infection.

This exemplifies what many such studies do; sample from the upper respiratory tract to find signs of replicating virus in order to study a disease of the lower respiratory tract. 

It's a stretch but if you go along with it you are implying that an upper respiratory tract infection either triggers the symptoms from afar or that the virus travels into the lower respiratory tract to directly cause inflammation and/or cell destruction.

Viruses were detected by PCR-based methods.

Some key findings...

• Respiratory syncytial virus (RSV) was the virus detected most often (51/102 samples from 153 children) in children who were admitted with wheezing followed by rhinoviruses (RV; 21 or 14%), RSV+RV (12 or 8%) and then parainfluenza virus 3 (PIV3; 8 or 5%), influenza virus (IFV; 5 or 3%) or human metapneumovirus (hMPV; 5 or 3%)
• A similar pattern was observed in 259 children who were admitted without wheezing (RSV-25%; RV 9%; IFV 7%; RSV+RV-4%; PIV3-3%; hMPV-1%)
• 67% of children with wheezing were virus positive (POS)
• Children with an allergic predisposition (IgE antibody levels >30IU/mL at admission and a parental history of asthma) POS for RSV more often had wheezing later
• Children who were wheezing & RV POS when they were admitted were more likely to wheeze again than were those who were RV POS without wheeze at admission.

So [allergic predisposition + RSV] or [wheeze/clinical severity + RV] were 2 factors related to subsequent wheeze.

The authors also raised the spectre of RV positivity occurring in asymptomatic individuals in other studies. However, that can happen to some extent with all respiratory viruses. No other virus has 160 distinct type like the RVs...but that's another story.

Article...

1. http://www.ncbi.nlm.nih.gov/pubmed/24535712

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Death of a young adult Qatari MERS patient who presented with flu-like illness...

So that last post is out of date already.

The Qatari Supreme Council of Health, as it does, has issued an announcement through the media (it has yet to update it's technically troubled website) announcing the death of the previously described 29-year old male with asthma who had been confirmed by an international (presumably UK-based) reference laboratory.

Asthma occurs in about 5% of the world's population, but in higher proportions in particular countries and regions.

This moves the deaths up to 54 with data, possibly 56 in total (see earlier post today for what that means) with a PFC of 48.3% for 56 deaths.

The presentation of this case on August 17th, was of "flu-like illness" which can be anything from fever + cough to much more. What this case highlights, and it is only a single case, is that cases can present with standard upper respiratory tract infection (flu most often starts off that way) which will make it devilishly hard to discriminate from that caused by many other non-MERS-CoV respiratory viruses. In a study of pilgrims leaving the 2012 hajj, 41% had flu-like symptoms (cough, sore throat and fever). I mentioned this in an earlier post (see #3 in the Prof Memish lit review) and the paper in Feb this year from Clinical Microbiology and Infection can be found behind a paywall here. A subsequent article published in Clinical Infectious Diseases this July, also paywalled and by the same group showed that a number of respiratory viruses were lab-confirmed as acquired while in the Kingdom of Saudi Arabia (showed symptoms of  illness), fewer were brought into the country and fewer were taken out. Not much can be concluded from that as I would expect this in any group tested in this way under these circumstances (travelling to a gathering of lots of people from around the world and from different climates  experiencing different respiratory virus seasons). It is not surprising that when you throw people together, they transmit respiratory infections and the the number of cases spikes.

This will be a big challenge if observation alone, rather than prospective laboratory testing, is used as a method to diagnose MERS among hajjis (thanks to AtRG for this phrase), in the coming weeks.

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A drug to stop rhinovirus (HRV) infections in patients with chronic obstructive pulmonary disease (COPD)?

For those who don't know, the HRVs are the most frequent infecting agents (that we know of) of the human upper (and perhaps lower but that work is not done) respiratory tract (URT).The first HRV was isolated in 1953 in the UK and the viruses were soon burdened by the label "common cold viruses". This was largely because early studies were conducted in adults who generally have milder outcomes.
There are about 77 genetically distinct HRV-As, 60 HRV-Cs and 30 HRV-Bs - that's nearly 170 distinct viruses (includes serotypes and genotypes)! Imagine 170 distinct coronaviruses.

In the past they were classified by the type of cell they infected/receptor they used into major (most of them used ICAM-I as the receptor) and minor (the rest; use VLDL-R as the receptor) groups. Sequencing is the preferred method to classify them today.

The receptor for the HRV-Cs remains unknown and they do not grow in routine cell lines instead needing more advanced culture methods. Because of this, studies predating 1988 (the first published PCR primers) generally don't account for the HRV-Cs, even though they were there and causing infections.

A.Prof Eva Kathryn Miller and I recently reviewed the HRV-Cs in some detail. Around 70 distinct HRV genotypes can circulate at a single place over a year...depending on the population being studied. I and others have found that to be the case in both the community and in hospital-based populations.

A recent article from Yamaya and colleagues suggests that a mucolytic drug (stimulates surfactant production and release to help the airways clear themselves of gunk) might be of use in treating HRV infections in COPD patients at least.

Exacerbations, which are mostly due to viruses, are the main contributor to disease burden in patients suffering from COPD, as they are in those with asthma.

The drug, ambroxol hydrochloride is already thought to reduce the frequency of URT disease and may reduce ICAM-I expression. The authors tested this using a major group HRV, HRV-B14 and found reduced release of virus, ICAM-I levels and reduced viral RNA levels.

Prophylactic use may inhibit HRV-B14 infection and modulate the inflammatory response to infection. Many of the differences were moderate (mostly arithmetic rather than logarithmic), albeit statistically significant.

It would be interesting to see what effect the drug has on other major group HRVs, minor group HRVs and on the hard to culture HRV-Cs.

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