IS ASTHMA A COMORBIDITY OF OBESITY?

The increased incidence of obesity in the United States during the last 30 years may explain at least part of the concomitant increase in asthma incidence, according to data from a large study published in the Archives of Internal Medicine. The findings indicate a strongly significant positive association between weight-as well as weight gain after age 18 years-and the risk of developing adult-onset asthma.

The researchers used data from the second Nurses' Health Study to determine if body mass index (BMI) and weight change are related to the risk of asthma. The cohort included 85,911 women, ages 26 to 46 years, who were enrolled in the study from 1991 to 1995.

During 4 years' follow-up, the researchers identified 1,596 incident cases of asthma. Multivariate analysis showed a significant, independent, and positive association between the baseline BMI measurement and the risk of adult-onset asthma; this association held even after adjustment for potential confounding factors.

The adjusted relative risk of asthma was 1.1 for a BMI of 22.5 to 24.9; 1.6 for a BMI of 25.0 to 27.4; 1.7 for a BMI of 27.5 to 29.9; and 2.7 for a BMI of 30.0 or greater (a BMI of 20.0 to 22.4 was used as the reference point). The relationship was found in a variety of subgroups and became stronger when stricter criteria for asthma were used.

Furthermore, the researchers found that women who had gained weight after age 18 years were at a markedly greater risk of developing asthma than were women who maintained a normal weight. In fact, 26% of the overall incidence of asthma in this study could apparently be accounted for by a weight gain of 2 kg or more since age 18 years.

The magnitude of the relative risk for asthma associated with obesity "is larger than that of many putative asthma risk factors and, when combined with the high prevalence of obesity in the United States, suggests that obesity may explain much of the current asthma epidemic," the researchers wrote.

Camargo CA Jr, Weiss ST, Zhang S, et al. Prospective study of body mass index, weight change, and risk of adult-onset asthma in women. Arch Intern Med. 1999;159:2582-2588.


BRONCHIOLITIS-ASSOCIATED HOSPITALIZATION INCREASES AMONG INFANTS

Bronchiolitis-associated hospitalization rates among infants increased significantly between 1980 and 1996. Because bronchiolitis is a hallmark of respiratory syncytial virus (RSV) infection, the findings reinforce the need for a safe and effective vaccine for RSV, researchers reported in a recent issue of JAMA.

Before this study, the only national estimate of hospitalizations associated with RSV infection had been made in 1985. According to those figures, an estimated 54,697 infants younger than age 1 year and 36,465 children ages 1 through 4 years were believed to be hospitalized for bronchiolitis or pneumonia associated with RSV each year in the United States.

The current study was designed to update those estimates. The researchers used data from the National Hospital Discharge Survey to identify children younger than age 5 years who were hospitalized in short-stay, nonfederal hospitals for bronchiolitis from 1980 to 1996.

In this population, there were an estimated 1.65 million hospitalizations for bronchiolitis-accounting for 7.0 million inpatient days-during the 17-year study period. Most of these hospitalizations (81%) occurred among children younger than age 1 year, and 57% occurred among children younger than age 6 months.

The annual number of bronchiolitis hospitalizations increased among children in each age-group during the study period, with the most dramatic rise-a 239% jump-found among children younger than age 6 months. The annual rate increased by 152% among children younger than age 1 year but rose more slowly-by 77%-among children between the ages of 1 and 4 years.

In addition, the proportion of hospitalizations for lower respiratory tract diseases associated with bronchiolitis increased from 22.2% to 47.4% among infants younger than age 1 year between 1980 and 1996. Looking at total hospitalizations, this proportion increased from 5.4% to 16.4% during the study period. There was no significant change during the same period in hospitalization rates for other lower respiratory tract diseases.

The researchers estimated that 73,400 to 126,300 children younger than age 1 year were hospitalized for RSV-associated bronchiolitis or pneumonia annually during the period of 1994 to 1996. Thus, the current annual rate of RSV-associated bronchiolitis and pneumonia hospitalizations among infants younger than age 1 year is about 1.5 to 2 times greater than the 1985 projection of about 54,700.

The researchers noted that the increased hospitalization rate for bronchiolitis may be related to several factors, including trends in child care practices, changes in the criteria for hospitalization among children with bronchiolitis, or improved survival of premature infants at high risk for RSV-associated hospitalizations.

Shay DK, Holman RC, Newman RD, et al. Bronchiolitis-associated hospitalizations among US children, 1980-1996. JAMA. 1999;282:1440-1446.


POLLEN AND POLLUTION CONTRIBUTE TO ALLERGIC SENSITIZATION

Pollen appears to play a greater role than does air pollution in inducing sensitization, a recent study published in the Annals of Allergy, Asthma, and Immunology suggests.

To probe this issue, Italian researchers examined two groups of school-age children-one group living in downtown Genoa; the other, in rural areas of Genoa Province. The city group consisted of 284 children; the rural group, of 202 children. All were between the ages of 11 and 14 years, and each underwent a skin prick test. The two groups were not significantly different in terms of their genetic risk factors for allergies. In both geographic areas, pollen counts were performed at the peak of the pollen season (July through August, 1996); ozone and suspended particulate levels were measured from April to September, 1996.

Overall, the rural group had a significantly higher frequency of sensitization than did the city group (46.0% vs 36.6%). Sensitization to pollen was more common in the rural areas, but pet sensitization was more frequent in the city. More rural children were sensitive to multiple allergens.

Interestingly, there was a markedly greater proportion of monosensitized subjects in the city group than in the rural group (37.5% vs 22.6%). The researchers offered a possible explanation for this finding, noting that mite allergy is prevalent in monosensitized individuals and occurs early in childhood, whereas pollen allergy is prevalent in polysensitized individuals and occurs later in childhood.

The researchers hypothesized that between-group differences in sensitization may be due to the different pollen exposure levels but noted that some studies have shown no differences between the proportion of sensitized individuals in rural and urban areas.

Crimi P, Boidi M, Minale P, et al. Differences in prevalence of allergic sensitization in urban and rural school children. Ann Allergy Asthma Immunol. 1999;83:252-256.


AIRWAY OBSTRUCTION AND THE SYSTEMIC EFFECT OF INHALED STEROIDS

The degree of airway obstruction in patients with asthma may alter the systemic bioavailability of inhaled glucocorticoids, according to findings published in a recent issue of Chest. Awareness of the degree of airway obstruction may help physicians optimize asthma control while lowering the risk of systemic adverse effects, the study authors suggested.

None of the 28 patients with mild to moderate asthma enrolled in this study had used oral or inhaled corticosteroids within the previous 3 months. All were receiving rescue treatment with ß₂-agonists only. Forced expiratory volume in 1 second (FEV1) was measured just before inhalation of either placebo (8:00 PM on day 1) or 500 µg fluticasone propionate (8:00 PM on day 2). Blood samples for cortisol measurement were then taken hourly from 10:00 PM to 6:00 AM the following morning.

In comparison with placebo, fluticasone reduced the mean early morning rise in cortisol secretions, and it decreased the total nocturnal cortisol production by 29.4%. The extent of the fall in cortisol production on the second night correlated significantly with the FEV1 measurement taken before the fluticasone inhalation. However, the FEV1 measurement taken before the placebo dose did not correlate with the patients' baseline cortisol production, nor did baseline cortisol production correlate with the second night's cortisol suppression.

Both the clinical efficacy and the systemic adverse effects of inhaled glucocorticoids are presumed to be dose related. However, the doses at which the risks of adrenal suppression outweigh the benefits of any of these drugs are unknown and may vary from patient to patient because of individual differences in tissue sensitivity and the severity of the underlying disease. The present findings point to the possibility that-at least for fluticasone-the optimal dose is also related to the degree of airflow obstruction, the researchers noted.

Weiner P, Berar-Yanay N, Davidovich A, Magadle R. Nocturnal cortisol secretion in asthmatic patients after inhalation of fluticasone propionate. Chest. 1999;116:931-934.

HIGHLY INFECTIOUS CHILD WITH TUBERCULOSIS

One child with extensive bilateral cavitary pulmonary disease transmitted Mycobacterium tuberculosis to 56 people-about 20% of his contacts. This suggests that children with tuberculosis should be considered potentially infectious; screening of their contacts may be required.

As reported in the New England Journal of Medicine, a 9-year-old boy was identified (in July 1998) as having infectious tuberculosis. The boy lived in a rural area of North Dakota, which has a low incidence of tuberculosis. A total of 276 of the child's contacts underwent tuberculin skin tests in mid-July, with follow-up screening about 12 weeks after their last exposure to the infected child.

A positive test result (ie, an induration of at least 10 mm) was found in 56 contacts (20%). Among the contacts were three of the child's four household members, 16 of his 24 classroom contacts, 10 of his 32 fellow school-bus riders, and 9 of his 61 day-care contacts.

Preventive therapy with isoniazid was given to 110 people, including 64 persons with skin test indurations of 5 mm or more. The remaining 56 persons given treatment were all children younger than age 6 years who had negative skin test results; they received preventive therapy anyway because of the high rate of positive results found among their peers.

"This outbreak was unusual because most children younger than age 10 years who have active tuberculosis are not infectious," the researchers said. The child's illness was most likely due to endogenous reactivation; he was born in an area of the Marshall Islands that has a high incidence of tuberculosis, the researchers noted. They believe that this outbreak might have been prevented if the child had been screened for tuberculosis and given appropriate preventive therapy upon his arrival in the United States in 1996.

Curtis AB, Ridzon R, Vogel R, et al. Extensive transmission of Mycobacterium tuberculosis from a child. N Engl J Med. 1999;341:1491-1495.


NEW APPROACHES TO MANAGING PPH

Oral administration of beraprost sodium may increase survival in patients with mild forms of primary pulmonary hypertension (PPH). According to a new study recently published in the Journal of the American College of Cardiology, beraprost (a newly developed prostacyclin analogue) may become an alternative to intravenous epoprostenol infusions.

Continuous intravenous infusions of epoprostenol have produced sustained clinical benefits and improved long-term survival in patients with PPH. However, this treatment is expensive and uncomfortable for many patients. In a previous study, the researchers found that beraprost reduced pulmonary vascular resistance in PPH patients. The present study was designed to determine whether the oral agent improves survival in outpatients discharged after the first diagnostic catheterization for PPH.

The study population consisted of 34 patients treated with conventional therapy alone (ie, calcium antagonists, nitrates, digitalis, and diuretics) and 24 patients treated with beraprost in addition to conventional therapy. Beraprost's initial strength was 60 µg/d; the dosage was increased over 1 or 2 weeks until the highest tolerated dose was reached (range, 60 to 180 µg/d). The total amount of the drug was administered in three or four doses per day.

At baseline, there were no significant between-group differences in demographics, hemodynamics, or pulmonary function. During a mean follow-up of 44 months, 27 patients in the conventional therapy group died of cardiopulmonary causes; in contrast, only four patients died of such causes in the beraprost group during a mean follow-up of 30 months. In a subset of 15 patients treated with beraprost and followed for a mean of 53 days, the mean pulmonary arterial pressure and total pulmonary resistance decreased significantly by 13% and 25%, respectively.

In multivariate analysis, increased mortality was independently related to two variables: the absence of beraprost therapy and reduced cardiac output. Survival rates (as measured by Kaplan-Meier curves) at 1, 2, and 3 years were 96%, 86%, and 76%, respectively, in the beraprost group, compared with 77%, 47%, and 44%, respectively, in the conventional therapy group.

In a related study (reported in the same journal), researchers found that patients who had developed high cardiac output states after being treated with excessive doses of epoprostenol experienced a return to normal cardiac output when doses were reduced-without an accompanying exacerbation of PPH. In that study, 12 PPH patients treated with chronic prostacyclin therapy (for a mean of 39 months) developed increased cardiac output (mean, 10.1 L/min), and such side effects as jaw pain, diarrhea, flushing, rash, and foot pain. The patients' epoprostenol doses were reduced under hemodynamic guidance to achieve a cardiac index of 4 L/min/m2 or lower.

After the mean dose was reduced from 98 to 60 ng/kg/min, the mean cardiac output decreased to 7.4 L/min, and the mean pulmonary vascular resistance increased from 3.7 to 4.7 units. Rebound pulmonary hypertension was not found in any of the patients, and the mean pulmonary arterial pressure increased only slightly (from 45 to 46 mm Hg).

After an average follow-up of 13.6 months, two patients required no further changes in dose, three patients required further dose reductions on an outpatient basis, and six required minor dose increases. "In addition, every patient described an improvement in the side effects of flushing, bloating, and fatigue related to prostacyclin, with some noting a dramatic reduction in the severity in their leg pain, or severity of their rash," the researchers reported.

Nagaya N, Uematsu M, Okano Y, et al. Effect of orally active prostacyclin analogue on survival of outpatients with primary pulmonary hypertension. J Am Coll Cardiol. 1999;34:1188-1192.
Rich S, McLaughlin VV. The effects of chronic prostacyclin therapy on cardiac output and symptoms in primary pulmonary hypertension. J Am Coll Cardiol. 1999;34:1184-1187.