Bronchiolitis rates increase

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Infectious Diseases in Children

Bronchiolitis rates increase, treatment has changed little over the

last few decades

Part of the increase in bronchiolitis probably is due to the

survival of more and more low- and extremely low-birth weight

infants who seem to be particularly prone to bronchiolitis.

by Philip A. Brunell, MD

Chief Medical Editor

February 2006

Philip A. Brunell

If you live in the north, it is about that time of year for

bronchiolitis. If you live in the southeast, you are already well

into the season.

It has been estimated that as many as 3% of infants are hospitalized

each year with bronchiolitis, and the incidence of this disease has

almost doubled in the past few decades. The increase has been most

marked in those younger than 6 months of age. It is also estimated

that there are, on average, 123,471 bronchiolitis hospitalizations

annually among children younger than 1 year and 154,365 among

children younger than 5 years; 50,000 to 80,000 were due to

respiratory syncytial virus (RSV) (JAMA. 1999;282:1440-1446).

If one adds the hospitalization rates for this and gastroenteritis,

it would appear that almost one in 25 infants born each year are

hospitalized for these two conditions alone, assuming no one infant

is unfortunate enough to be hospitalized for both. I find these

figures incredible. Part of the increase in bronchiolitis probably

is due to the survival of more and more low- and extremely low-birth

weight infants who seem to be particularly prone to bronchiolitis.

Low-birth weights increased from 6.7% in 1984 to 8.1% in 2004, a 21%

increase (Pediatrics. 2006;117:168-183). However, this increase

could not in itself account for the rise in cases of bronchiolitis.

When I was a resident assigned to newborn service before the

neonatal ICU with lots of time on my hands, I decided to review the

pathology reports of children dying of bronchiolitis. In spite of

the fact that the wards were filled with these children every

winter, very few made it to the pathology department despite the

fact that the hospital had a 90% autopsy rate. In fact, most writers

referring to the pathology of bronchiolitis still cite the

descriptions of decades ago. Indeed, examination of material

collected in more recent years may be complicated by therapeutic

interventions. Although classical pathologic descriptions do not

change, we now have sophisticated tools to elucidate the

pathogenesis of this disease. In recent years, there has been an

increasing interest in studying these (Arch Ped Adol

Med.2004;158:111-112).

Unfortunately, not only has the basic pathology changed little, the

same can be said of our treatment of this condition. In the 1950s,

during my residency, we designed a trial to determine whether

steroids would be beneficial in babies with bronchiolitis. This

involved the " high-tech " use of cameras to evaluate breathing in

effort not to introduce an artifact and disturb the infant.

The tapes could have been evaluated blindly to maintain objectivity.

We are all guilty of bias when we use a treatment. Since this time,

there have been countless studies — some of which have been

reported — to evaluate several modalities for treatment. Most of

these have been used in the management of asthma, which is a poor

model on which to base interventions. These include steroids, ß

agonists, epinephrine given by various routes and, most recently,

helium. The endpoints have varied from improvement in physiologic

parameters and more relevant ones (eg, earlier discharge or need for

intubations or intensive care).

A number of meta-analyses (Arch Ped Adol Med. 2004;158:127-137) have

come to essentially the same conclusion for most of these

treatments. That is, there may be a transitory improvement in

physiologic parameters, but in achieving the critical objectives,

there has been little perceptible difference. (Brunell rule #46.32 —

If it takes half a century to determine whether an intervention is

effective, it probably is not.) Many try something, usually

epinephrine, in the hope that it may " help a subset. "

My question is, will it harm a subset? Meta-analysis has shown that

some patients may be harmed by these interventions (Arch Pediatr

Adolesc Med. 2004;158:127-137). Ribavirin, for which we had hopes a

few seasons ago does have potential toxicity. One of the caveats

applying the lessons from these trials is that most have been done

in hospitalized severely ill patients rather than patients likely to

be seen in the office. Clearly, we need a radically different

approach to treatment.

The greatest advancement has been the use of passive immunization to

prevent RSV-caused bronchiolitis in high-risk infants. Palivizumab

(Synagis, MedImmune) is the standard of care for certain infants.

This preparation is a humanized monoclonal antibody that binds to

the F antigen of RSV. It has shown to be effective in reducing

bronchiolitis hospitalizations in those infected with RSV by 55% as

well as decreasing hospital stays and the need for supplemental

oxygen (Pediatrics. 1998; 102:531-537). It will probably be more

effective during the RSV season than other times of the year when

parainfluenza and other viruses are responsible for a significant

number of cases of bronchiolitis. It is not effective against human

metapneumoviruses, which cause about 10% of cases of bronchiolitis;

their season usually overlaps with the RSV season. The

recommendations for palivizumab use have been updated to include

patients with significant cardiac disease (Pediatrics. 2003;112:1442-

1446). Palivizumab is very expensive and labile, so infants should

be cohorted to use the material as efficiently as possible once the

vial has been opened. Cost is a major consideration in infants born

between 32 and 35 weeks gestation. Additional factors, such as

impairment of ventilation and exposure to tobacco smoke, should be

considered when weighing the decision for use in this group. It is

necessary to emphasize the need to eliminate the exposure to tobacco

smoke. Spread of RSV occurs readily and attention to hand washing is

applicable in every situation.

Since RSV first was isolated many decades ago, there have been

multiple attempts to prevent infection by active immunization. The

initial attempt — using a killed vaccine — was an utter failure as

RSV vaccine recipients had more severe disease following exposure to

RSV than those who had been given parainfluenza vaccines; the attack

rates were similar. (Am J Epidemiol. 1969;89:422-434). This

experience was, needless to say, very discouraging and probably a

retarded progress for some time. However, there have been vaccines

since that time (eg, subunit F and G components and intranasal live

vaccines that have shown some promise). As the most severe disease

occurs early in infancy, immunization must occur as soon after birth

as possible. Parenterally administered live vaccines are inactivated

by maternal antibodies, which are highest postpartum. The intranasal

candidates have shown promise, but the early generations have caused

nasal stuffiness in some young infants, which is a major problem in

this age group as they are obligatory nose breathers.

There are two areas that I think bear looking into. We are

continuing to learn more about the innate immune responses (ie, the

immediate response to infection that is manifested mainly by

inflammation). We need to identify the specific factors involved in

the pathogenesis of bronchiolitis and how they might be modified by

therapy. Steroids are not doing it. In addition, we need to study

the differences in responses of those infants who are infected with

RSV and contract bronchiolitis and those who just get an upper

respiratory infection or a fever when infected with the same virus.

By the second year of life, most infants already have been infected,

yet only a fraction presents with significant illness. Clearly, some

of the differences in clinical expression are due to size of the

airways. That, however, does not explain the occurrence of

bronchiolitis in full-term or older infants.

RSV does not pick out the bronchioles; it involves the entire

respiratory system, hence the high rate of otitis in children with

RSV bronchiolitis. Finally, we should not forget that the nasal

passages are part of the affected respiratory tract and, even when

unaffected, produce a significant portion of airway resistance. I am

impressed how many writings on this subject totally ignore the nose

and proceed directly to the lungs.

In addition to inflammatory cells and debris, which occlude the

airways, diminish their size and increase resistance to air flow,

turbulence also is increased. Nasal exudates, which are present in

almost all infants with bronchiolitis, are particularly important in

obligatory nose breathers with a small nasal airway diameter. One of

my " low-tech " approaches is to clean the nose of an infant who has

bronchiolitis with an infant nasal aspirator, not an ear aspirator,

which does not enter the nasal cavity and causes more inflammation

and slides right past much of the obstructing secretions. I have

been impressed how frequently, when I have returned a few minutes

after this procedure, how the respiratory rate has decreased. You

might want to try it on infants whom you are uncertain as to whether

hospital admission is indicated. It is cheap, innocuous and likely

to work. I have included a table that appeared in a British

publication on criteria for office guidance on the management of

infants with bronchiolitis (Arch Dis Child. 2005;90:ep81-ep86).