Vanguard Neurologist

From www.nytimes.com
A decline in aspirin use, exposure to household sprays and cleaners and lack of vitamin D may all help explain surging asthma rates in the past few decades.

For years the hygiene hypothesis has been used to explain stark differences in asthma rates around the world. In Western countries, asthma rates are about 50 times higher than in rural Africa, for instance. The hygiene hypothesis suggests that Westerners have less exposure to bacteria, viruses and parasites, altering the immune response and increasing risk for allergic diseases.

But Dr. Harold S. Nelson, professor of medicine at the asthma and allergy specialty hospital National Jewish Health in Denver, says the hygiene hypothesis doesn’t fully explain rising asthma rates in the United States and industrialized countries. The incidence of asthma has doubled in the United States since the 1980s.

In a recent talk at National Jewish Health’s annual Pulmonary and Allergy Update conference, Dr. Nelson noted that lower levels of vitamin D, exposure to spray cleaning compounds, and a wider use of acetaminophen in place of aspirin have contributed to the asthma epidemic.

The concern with household cleaners is that the spray mist can be inhaled and irritate the lungs, increasing risk for asthma. The biggest culprits appear to be glass cleaners and air fresheners. A major European study of cleaning product use in 10 countries found that people who used the cleaners four days a week faced double the risk of adult asthma. Weekly use increased risk by 50 percent. Australian researchers have also found a link with household cleaning sprays and asthma in children.

In a November 2007 article in The Journal of Allergy and Clinical Immunology, researchers from Brigham and Women’s Hospital in Boston reviewed the evidence showing a link between low vitamin D levels in mothers and childhood asthma. The authors wrote:

We hypothesize that as populations grow more prosperous, more time is spent indoors, and there is less exposure to sunlight, leading to decreased cutaneous vitamin D production. Coupled with inadequate intake from foods and supplements, this then leads to vitamin D deficiency, particularly in pregnant women, resulting in more asthma and allergy in their offspring.

Declining aspirin use may also help explain rising asthma rates. Young children should not be given aspirin because it increases risk for Reye’s syndrome. But a common alternative, acetaminophen, the ingredient in Tylenol, may increase a child’s risk for asthma when used in very young children or in high doses. The drug lowers levels of the antioxidant glutathione, which can help protect against lung damage caused by oxidants. In a study of more than 200,000 6- and 7-year-olds, use of acetaminophen in the first year of life was associated with a 46 percent increase in prevalence of asthma symptoms. Children using higher doses of acetaminophen had three times the risk of asthma.

Dr. Nelson notes that the research isn’t conclusive, but that people can take simple measures to lower their exposure to these new risk factors. Use liquid cleaners or pump sprays that don’t generate a fine mist. Eliminate use of spray air fresheners. Pregnant women and mothers should talk to their obstetricians and pediatricians about whether they should consider vitamin D supplements. And parents should discuss pain relievers with the pediatrician. Every pain reliever carries risks, and alternatives to Tylenol like ibuprofen can increase risk for gastrointestinal complaints. However, doctors may recommend switching between pain relievers or limiting exposure to acetaminophen in certain cases.

“There is a lot of supporting evidence for all three of these new risk factors,” Dr. Nelson said.

From medpagetoday.com
Asthma prevalence begins to switch genders at the onset of puberty, when the condition becomes more common in girls, researchers here said.

Action Points
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Explain to interested patients that more boys than girls have asthma during early childhood, but in adulthood asthma is more common among women than men.

Explain that this study suggested that the gender difference reverses at about age 11 to 12, coinciding with onset of puberty.
In a study of 1,041 asthmatic children tested annually over a nine-year period, 11 was the last age at which airway responsiveness to methacholine challenge was not enhanced in girls relative to boys, reported Kelan Tantisira, M.D., M.P.H., of Brigham and Women’s Hospital, and colleagues, in the Aug. 15 issue of the American Journal of Respiratory and Critical Care Medicine.

At age 12, boys required 3 mg/ml of methacholine to produce a 20% decrease in forced expiratory volume, whereas girls needed only 2 mg/ml, after adjusting for potential confounding factors. At age 10, 20% reductions in forced expiratory volume were achieved with 2 mg/ml in boys as well as girls.

Although the researchers did not have direct data on hormonal changes in the children, the emerging gender difference appeared to coincide with onset of puberty.

Dr. Tantisira said the findings may help clinicians do a better job of managing asthma in adolescent patients. They also give new clues to the mechanisms underlying the well-known female predominance of adult asthma.

In young children, asthma and wheezing are well known to be substantially more common in boys than girls, but the gender differences reverse by the time they become adults.

The current study provides the first year-by-year data showing when the tide turns, Dr. Tantisira said.

Participants were five to 12 years old at enrollment and were predominantly white (68%) and male (60%). Asthma symptoms were generally mild to moderate at baseline.

The study began as a randomized trial of budesonide (Pulmicort) versus nedocromil sodium (Tilade) for four to six years. Following the formal trial, 941 participants continued for up to five additional years in an observation phase with asthma treatment based on standard guidelines directed by their personal physicians.

The children underwent methacholine challenge testing every year for a mean of 8.6 years (SD 1.8).

When Dr. Tantisira and colleagues correlated the results with the level of participants’ physical maturation, as measured by Tanner stage, they found that airway responsiveness began to diverge between boys and girls at stage 3.

Differences were minimal at stages 1 and 2. At stage 3, mean adjusted methacholine doses separated to about 2.7 mg/ml in boys versus 2.0 mg/ml in girls, but the confidence limits overlapped.

For participants at stage 4, the mean adjusted methacholine doses were 3.1 mg/ml in boys and 1.8 in girls. The gap continued to widen linearly at stage 5 (P=0.0002 for trend).

Adjustments in these analyses include baseline factors such as clinic, race, duration, and severity of asthma, positive skin test, and recent inhaled corticosteroid usage.

Dr. Tantisira and colleagues also identified several factors that predicted increased airway responsiveness only in girls, not boys:

History of hay fever: beta -0.30, P=0.005
Respiratory allergy: beta -0.32, P=0.006
Recent inhaled corticosteroid use: beta -0.18, P=0.02

However, these relationships were not strong enough to explain the differences from boys from age 12 onward.

The researchers said the correlation between Tanner stage and responsiveness is probably related to hormonal changes, specifically involving estrogen and progesterone.

They dismissed dysanapsis — the differential growth rates affecting lung size and airway size — as a likely mechanism because gender differences reach a peak at about age 18.

Dr. Tantisira said the study’s most important implications would come from long-term exploration of the mechanisms underlying the gender difference.

But they could also help clinicians now, he said.

“One of the things we have a hard time with is knowing when to stop medications,” he said.

He suggested that clinicians could begin to handle dosage adjustments differently in boys versus girls when they enter adolescence.

For boys who report few or no episodes, he said, physicians could try halting maintenance medication altogether, whereas “a more gradual approach” may be more prudent for girls.

In an accompanying commentary, Jorrit Gerritsen, M.D., Ph.D., of the University of Groningen in Holland, called the study “fascinating.”

He said following the participants into adulthood could be even more informative.

A smaller study at his own institution has been tracking pediatric asthma patients to age 40 and beyond. Dr. Gerritsen said the largely male cohort continued to show decreases in airway responsiveness through their twenties, but many then had a resurgence in symptoms in their 30s.

He recommended that Dr. Tantisira and colleagues follow their cohort “for as long as possible since these individuals offer a unique opportunity that may provide insight in the natural course of asthma both in male and female subjects.”

Dr. Tantisira and colleagues said the lack of direct hormonal measures in the study was an important limitation.

They also said the treatment assignments during the randomized-trial phase might have affected the results. But they said it was unlikely since airway responsiveness was similar in the two treatment groups following drug washout at the end of the trial.

The study was funded by the National Institutes of Health. Co-authors on the study reported past or present relationships with AstraZeneca, Boehringer Ingelheim, Genentech, Roche, Pfizer, Schering-Plough, Variagenics, Genomic Therapeutics, Merck Frosst, GlaxoSmithKline, Sepracor, and Merck. Dr. Gerritsen reported no potential conflicts of interest.

Primary source: American Journal of Respiratory and Critical Care Medicine
Source reference:
Tantisira K, et al “Airway responsiveness in mild to moderate childhood asthma sex influences on the natural history”Am J Respir Crit Care Med 2008; 178: 325-31.