AIRWAY STRUCTURE IN FATAL ASTHMA

Smooth muscle contraction and production of an inflammatory mucus exudate play a role in fatal asthma attacks, new findings suggest. The data also support the hypothesis that the duration of asthma is associated with progressive airway wall remodeling, reported Bai et al.

The researchers examined lung tissue from 27 randomly selected cases of fatal asthma. Fourteen subjects were age 17 to 23 years at the time of death, and 13 were age 40 to 49 years. Airway dimensions from the patients with fatal asthma attacks were compared with those from 11 controls (five young and six older subjects who died in motor vehicle accidents).

The average wall area was similar among young and older controls. Among those with fatal asthma, however, it was about three times higher in the older than in the young patients. This difference was mainly caused by a greater adventitial area in the older patients.

Regardless of age, the patients with fatal asthma had greater connective tissue matrix around smooth muscle cells than did control patients. However, smooth muscle area was only twofold larger in the young asthma patients than in the young controls--but fourfold larger in the older asthma patients than in the older controls.

Both age and asthma severity influenced the extent of airway narrowing. Among those with fatal asthma, airway narrowing was more marked in the older than in the young patients, but both subgroups had increased airway narrowing compared with age-matched controls.

In addition, both subgroups of asthma patients also had significantly greater intraluminal obstruction (from luminal mucus-debris) and subepithelial collagen thickness than did control subjects, but this effect did not vary by age. In fact, the findings suggest that "it is very uncommon to die [of asthma] without substantial luminal obstruction," the researchers concluded.

Overall, wall dimensions were not significantly different between young patients with fatal asthma and age-matched controls but were significantly increased in older asthma patients versus older controls, Bai et al reported. "These results suggest that with increased duration of asthma there is ongoing remodeling with an increase in airway tissue" and that factors other than airway dimensions contribute to the pathogenesis of fatal asthma in young patients, according to the study authors.

Bai TR, Cooper J, Koelmeyer T, et al. The effect of age and duration of disease on airway structure in fatal asthma. Am J Respir Crit Care Med. 2000;162:663-669.

COST-EFFECTIVE RSV CONTROL PROGRAM

A hospital-based infection-control intervention is a cost-effective approach to preventing the transmission of respiratory syncytial virus (RSV) infection, Macartney et al found in a recent case-control study.

The researchers compared the number of RSV cases that occurred in the four years before and after initiation of an RSV infection-control program. The components of the intervention are listed in Table 1.

Table 1 Components of an RSV Infection-Control Intervention

Educate staff Confirm cases of RSV infection Use contact precautions Isolate RSV patients in a separate room Designate nursing staff to care only for isolated RSV patients Discourage staff with symptoms of RSV infection from working in the intensive care unit or with immunocompromised patients; encourage staff with RSV symptoms to wear a mask when caring for other patients Restrict visits from family members with RSV symptoms Appoint infection-control staff to monitor compliance and alert nursing unit managers of nosocomial RSV cases

Data extracted from Macartney et al. Pediatrics. 2000. RSV, respiratory syncytial virus.

The rate of nosocomial RSV infections was 39% lower in the postintervention period than in the preintervention period; this difference was statistically significant. The researchers estimated that the intervention prevented 10 RSV cases per season.

The cost of preventing a single case of RSV nosocomial infection was estimated to be $1,563, while the cost to the hospital for each patient with a nosocomial RSV infection was estimated to be $9,419 per case. Therefore, an estimated $6 was saved for every dollar spent on the infection-control intervention.

Macartney KK, Gorelick MH, Manning ML, et al. Nosocomial respiratory syncytial virus infections: the cost-effectiveness and cost-benefit of infection control. Pediatrics. 2000;106:520-526.

NEW PIGTAIL CATHETER FOR PULMONARY EMBOLISM

A new pigtail-shaped catheter designed to break up massive pulmonary emboli was found to be safe and effective in a recent trial. "This method appears useful, especially in high-risk patients threatened by right ventricular failure, to accelerate thrombolysis and as a minimally invasive alternative to surgical embolectomy," the researchers reported.

Schmitz-Rode et al designed a rotatable pigtail catheter and tested its efficacy in fragmenting massive pulmonary emboli in 20 patients with severe hemodynamic impairment. The average pulmonary arterial occlusion was 68.6%.

Fifteen patients received either thrombolysis after fragmentation or not at all (noninterference group). The remaining five patients received thrombolytic agents before catheter fragmentation was performed. Because the effects of fragmentation could not be separated from those of thrombolytic therapy, the data on these five patients had to be excluded from the primary analysis but were used to evaluate the overall feasibility and safety of the procedure.

In the noninterference group, the average shock index and the systolic, diastolic, and mean pulmonary artery pressures decreased significantly following fragmentation. The mean percentage of recanalization by fragmentation was 32.9%, and the mean angiographic severity score decreased from 7.4 to 5.0.

In the overall group, "pulmonary placement and navigation of the fragmentation catheter was easy and rapid from all approaches," Schmitz-Rode et al noted. The mean total procedure time was 44 minutes, and the mean fragmentation time was 17 minutes. Four patients (20%) died after the intervention.

Schmitz-Rode T, Janssens U, Duda SH, et al. Massive pulmonary embolism: percutaneous emergency treatment by pigtail rotation catheter. J Am Coll Cardiol. 2000; 36:375-380.

DO SIBLINGS OR DAY CARE REDUCE THE RISK OF ASTHMA?

Children who attend day care in the first six months of life or who have older siblings may be at reduced risk for developing asthma and frequent wheezing later in childhood, Ball et al have found. The researchers hypothesized that greater acquisition of respiratory infections during infancy may in some way protect against asthma and wheezing later in life.

The researchers followed a total of 1,035 children from birth to age 13 years. The subjects' parents completed questionnaires concerning their children's respiratory status at age 6, 8, 11, and 13 years. Children who had been diagnosed with asthma and who had experienced an asthma exacerbation in the previous year were categorized as having asthma. Frequent wheeze was defined as the occurrence of four or more wheezing episodes in the previous year.

Children living with one or more siblings had a significantly lower risk of developing asthma than did those with no siblings. In fact, each additional older sibling equated to a 20% reduction in the adjusted relative risk of asthma. Children who attended day care in the first six months of life had a significantly lower risk of asthma than did those who did not attend day care (adjusted relative risk, 0.4).

The presence of siblings and attendance at day care during the first six months of life were associated with a 40% increase in the risk of frequent wheezing at age 2 years, according to Ball et al. However, these two factors were associated with a 20% decrease in the risk of frequent wheezing at age 6 years, a 40% decrease at age 8 years, a 60% decrease at age 11 years, and a 70% decrease at age 13 years. Similar relationships were found when each variable was examined separately.

Ball TM, Castro-Rodriguez JA, Griffith KA, et al. Siblings, day-care attendance, and the risk of asthma and wheezing during childhood. N Engl J Med. 2000;343:538-543.

NOREPINEPHRINE FOR SEPTIC SHOCK

The vasopressor norepinephrine is more effective than high-dose dopamine in the treatment of septic shock in patients with persistent hypotension, a prospective observational study indicates.

Although previous studies have suggested that norepinephrine is an effective vasopressor, the drug has not been used regularly in septic shock patients because of the fear of excessive vasoconstriction and because hemodynamic monitoring is not always performed in such patients.

Data from 97 adults with septic shock were included in the analysis. Martin et al recorded 19 clinical, biological, and hemodynamic variables for each patient at study entry and determined which factors were associated with outcome.

All of the patients had persistent hypotension, oliguria, and lactic acidosis despite treatment with antibiotics, respiratory support, fluid resuscitation, and dopamine (5 to 15 µg/kg/min). The patients were then given either high-dose dopamine (16 to 25 µg/kg/min) or the lower dose of dopamine plus norepinephrine (0.5 to 5.0 µg/kg/min).

Those who were still hypotensive were given epinephrine. Patients whose hemodynamic status was stable for at least 24 hours were progressively weaned off of the drugs.

Overall, 70 patients (73%) died in the hospital. The following four factors were independent predictors of a poor outcome: pneumonia as a cause of septic shock, organ system failure index of three or more, urine flow below 10 mL/h at study entry, and lactate concentration above 4 mmol/h at study entry. On the other hand, use of norepinephrine was significantly associated with a decreased risk of hospital mortality. The mortality rates for patients treated with and without norepinephrine were 62% and 82%, respectively.

Martin et al acknowledged that their findings are limited by the study design, and thus they called for a randomized clinical trial to confirm the results.

Martin C, Viviand X, Leone M, Thirion X. Effect of norepinephrine on the outcome of septic shock. Crit Care Med. 2000;28:2758-2765.

CLOSURE OF PATENT DUCTUS ARTERIOSUS

Ibuprofen is as effective as indomethacin in the treatment of patent ductus arteriosus among preterm infants with respiratory distress syndrome, according to findings from a recent study. Furthermore, in this study, ibuprofen was less likely to cause renal dysfunction than was indomethacin.

A total of 148 preterm infants with respiratory distress syndrome and patent ductus arteriosus were randomized to three intravenous doses of either indomethacin or ibuprofen. The treatments were initiated three days after birth. At baseline, the two groups had similar clinical and echocardiographic characteristics.

Ductal closure occurred in a similar proportion of the two groups (70% in the ibuprofen group and 66% in the indomethacin group). The groups also had a similar number of infants who required a second pharmacologic treatment for ductus closure or surgical ductal ligation. The following four factors were significant independent predictors of treatment failure in the overall cohort: gestational age of 26 weeks or less, use of antenatal indomethacin treatment at 48 hours or less before birth, receipt of high-frequency oscillatory ventilation, and elevated pulmonary artery pressure.

The incidence of oliguria was significantly lower in the ibuprofen group (7%) than in the indomethacin group (19%). Otherwise, the two groups had a similar incidence of complications and other side effects, the researchers found.

Van Overmeire B, Smets K, Lecoutere D, et al. A comparison of ibuprofen and indomethacin for closure of patent ductus arteriosus. N Engl J Med. 2000;343:674-681.

STAGING NON-SMALL-CELL LUNG CANCER BY PET

Whole-body positron-emission tomography (PET) is more sensitive, specific, and accurate than computed tomography (CT) in the preoperative staging of non-small-cell lung cancer, according to data from a recent study. The findings showed that using PET scans improved the rate of detection for local and distant metastases.

Pieterman et al compared the results of standard approaches to staging (ie, CT of the chest, ultrasonography, bone scanning, and needle biopsy) with staging involving whole-body PET. They studied 102 patients with non-small-cell lung cancer who were undergoing preoperative evaluation. The PET scans were used to detect metastases in mediastinal lymph nodes and at distant sites. Biopsies were performed for all patients with signs or symptoms of distant metastases.

Compared with CT, PET had both a higher sensitivity (91% vs 75%) and specificity (86% vs 66%) in detecting mediastinal metastases. PET also had a high sensitivity and specificity in detecting distant metastases (82% and 93%, respectively). Furthermore, PET detected distant metastases that were not found on CT scans from 11 patients.

While both the CT and PET findings were significantly correlated with the results of histopathologic analysis, only the correlation with PET results remained significant after the researchers performed regression analysis. Clinical staging from PET results was different from that derived using standard approaches in 62 patients. In 42 patients, the stage determined by PET was higher than that arrived at by standard methods.

Pieterman RM, van Putten JW, Meuzelaar JJ, et al. Preoperative staging of non-small-cell lung cancer with positron-emission tomography. N Engl J Med. 2000;343:254-261.

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