REDUCED RISK OF ASTHMA AMONG TWINS

Twins are significantly less likely to have asthma than are singletons, Strachan et al have found. While the cause of this reduced risk is not clear, the authors suggested that the protective effect of twin births on allergic disease may be similar to the protective effect of large families.

All children born in Scotland from 1981 to 1984 were included in the analysis. Strachan et al analyzed rates of hospital admissions for respiratory disease among twins and singletons up to age 10 years.

As shown in Table 1, the overall admission rate for respiratory disease was significantly lower among twins than among singletons. This difference was attributable to a significantly lower risk of admission for asthma among twins. In contrast, the rate of admissions for acute bronchitis and bronchiolitis was significantly higher for twins than for singletons.

Strachan DP, Moran SE, McInneny K, Smalls M. Reduced risk of hospital admission for childhood asthma among Scottish twins: record linkage study. BMJ. 2000;321:732-733.

FEV6 CAN DIAGNOSE AIRWAY OBSTRUCTION

Forced expiratory volume in six seconds (FEV6) is an acceptable alternative to forced vital capacity (FVC) for diagnosing airway obstruction in adults. The use of FEV6 simplifies testing procedures, reduces test variability, and may improve accuracy in diagnosing airway obstruction.

Swanney et al studied 502 consecutive adult patients who were referred for routine spirometry, 337 (67%) of whom had technically acceptable tests for analysis. Each subject was judged to have "airway obstruction" or "no airway obstruction" on the basis of both FEV1/FVC (the gold standard) and FEV1/FEV6.

The latter measurement was found to have a sensitivity of 95.0%, a specificity of 97.4%, a positive predictive value of 98.6%, and a negative predictive value of 91.1%. Even after allowing for a measurement error of ±100 mL in FEV1 and FEV6, the authors discovered that only one patient would have had a discordant classification. Furthermore, FEV6 was much more reproducible than was FVC.

The authors note the following advantages to using FEV6 in place of FVC:

• Spirometry may be easier in older and impaired patients because they would not have to exhale as long.
• A shorter expiratory time means less data storage space.
• The end of the test is more clearly defined, permitting more reliable correspondence between measured and referenced values.

However, the authors caution that their findings apply only to adults who are able to exhale for six seconds.

Swanney MP, Jensen RL, Crichton DA, et al. FEV6 is an acceptable surrogate for FVC in the spirometric diagnosis of airway obstruction and restriction. Am J Respir Crit Care Med. 2000;162:917-919.

CHALLENGE TESTS FOR BRONCHIAL HYPERREACTIVITY

Methacholine (MCH) is as sensitive as adenosine 5´-monophosphate (AMP) for detecting bronchial hyperreactivity in children and young adults with mild to moderate asthma. According to a prospective study from Israel, both MCH and AMP are superior to exercise testing for this purpose.

Avital et al studied 135 children and young adults ages 6 to 25 years. Of these, 85 who used bronchodilators alone (on an as-needed basis) were considered to have mild asthma; 50 who required continuous prophylactic therapy were classified as having moderate asthma. All subjects underwent challenge for the detection of bronchial hyperreactivity with MCH, AMP, and exercise (running on a treadmill for six minutes).

Overall, the mean baseline forced expiratory volume in one second (FEV1) was 86.1% of predicted. Ninety-eight percent of the subjects responded to MCH at or before a cutoff of 8 mg/mL; 96% responded to AMP at 200 mg/mL or less. In contrast, only 65% of patients showed hyperreactivity to exercise when the cutoff was greater than 8.2% decrease in FEV1.

The mean provocation concentration of MCH causing a 20% fall in FEV1 was significantly higher among patients with mild asthma than among those with moderate disease. Further statistical analysis confirmed that MCH better differentiates between mild and moderate asthma than does AMP or the percentage fall in FEV1 after exercise.

Avital A, Godfrey S, Springer C. Exercise, methacholine, and adenosine 5´-monophosphate challenges in children with asthma: relation to severity of the disease. Pediatr Pulmonol. 2000;30:207-214.

ß-LACTAM USE IS STRONGLY ASSOCIATED WITH S PNEUMONIAE RESISTANCE

Outpatient ß-lactam use has been linked to decreased susceptibility of Streptococcus pneumoniae to penicillin. This finding emphasizes the importance of reducing inappropriate antibiotic administration.

Data relating to outpatient antimicrobial drug use were obtained retrospectively for the regions surrounding 23 American medical centers. The data included the number of prescriptions (per 100,000 population) written each month during the 48 months between May 1994 and April 1998. The 23 centers were classified according to high, intermediate, and low use for each class of antimicrobial agent. In addition, susceptibility testing was performed during two periods (1994-1995 and 1997-1998) to determine how effective penicillin and erythromycin were against S pneumoniae.

Overall, penicillin nonsusceptibility rose by 8.9% between the two test periods--the number of isolates that showed intermediate or complete resistance to penicillin increased from 22.2% to 31.1%. Erythromycin nonsusceptibility doubled, from 10.2% to 20.6%. When these results were compared with the data for antibiotic administration in the surrounding communities, the authors found that higher ß-lactam use was strongly associated with increased resistance to penicillin. Higher macrolide use was linked to decreased penicillin resistance. No significant association was found between antibiotic administration and the change in erythromycin resistance.

Diekema DJ, Brueggemann AB, Doern GV. Antimicrobial-drug use and changes in resistance in Streptococcus pneumoniae. Emerg Infect Dis. 2000;6:552-556.

DRUG IMPROVES RHINNORRHEA, SLEEP QUALITY

Azelastine significantly improves rhinorrhea and sleep quality in patients with perennial allergic rhinitis. Whether this nasal antihistamine also reduces daytime sleepiness and nasal congestion remains unclear.

Golden et al randomized 24 subjects with perennial allergic rhinitis to two sprays of placebo or azelastine twice a day for four weeks. The patients then crossed over to the opposite treatment for four more weeks. All patients made daily ratings of the severity of their rhinitis, using a scale from 0 (none) to 3 (severe). In addition, they maintained a daily diary in which they rated the severity of their nasal congestion, daytime sleepiness and fatigue, and nighttime sleep quality, using a scale of 0 (none) to 4 (severe).

During azelastine treatment, patients' assessment of the severity of their rhinorrhea dropped by a mean of 0.583; their rating of nighttime sleep quality improved by a mean of 0.912. Both changes were significant. In addition, active treatment was associated with nonsignificant improvements in nasal congestion and daytime somnolence.

Five patients withdrew from the study early, four of whom were taking azelastine when they left the study. The most common reason for discontinuation among these four patients was a worsening of sedation.

Golden S, Teets SJ, Lehman EB, et al. Effect of topical nasal azelastine on the symptoms of rhinitis, sleep, and daytime somnolence in perennial allergic rhinitis. Ann Allergy Asthma Immunol. 2000;85:53-57.

HOME POLYSOMNOGRAPHY: LOWER COST, BUT HIGHER FAILURE RATE

Home polysomnography is less expensive than laboratory testing for diagnosing sleep apnea syndrome. However, the poor quality of the data obtained at home raises questions about the feasibility of home testing, say the authors of a French study.

Portier et al performed both home and laboratory polysomnography on 78 patients; in each case, the order of testing was determined randomly. The mean respiratory disturbance index (RDI) was 25.7 during laboratory testing and 22.8 during home polysomnography. Moderate sleep apnea syndrome was defined as an RDI of 15 or higher; an RDI of 30 or higher was considered severe sleep apnea syndrome.

Laboratory testing detected sleep apnea in 37 patients; home testing suggested the diagnosis in 31 patients, 30 of whom had also been given the diagnosis during laboratory testing. Thus, there were discordant diagnoses in eight cases.

When home test results were compared with laboratory results, discordant RDI measurements (defined as a difference of more than ± 10. events per hour of sleep) were found 35% of the time--in 12 (22%) of the 54 patients with normal breathing or moderate sleep apnea and in 15 (63%) of the 24 patients with severe sleep apnea.

Although the subjects spent more time in bed at home than they did in the laboratory, their quality of sleep and number of awakenings did not differ between the two settings. Thirty-seven patients (48%) expressed a preference for laboratory polysomnography, 22 (28%) preferred home testing, and 19 (24%) had no preference.

The authors attribute the differences between the home and laboratory results primarily to recording conditions, noting that the home conditions were not standardized or controlled. They suggest that the 50% reduction in cost with home testing must be weighed against the high failure rate.

Portier F, Portmann A, Czernichow P, et al. Evaluation of home versus laboratory polysomnography in the diagnosis of sleep apnea syndrome. Am J Respir Crit Care Med. 2000;162:814-818.

MUSCLE TRAINING IMPROVES PERCEIVED DYSPNEA

Patients with chronic obstructive pulmonary disease (COPD) show a greater improvement in perceived dyspnea after inspiratory muscle training than after treatment with a long-acting bronchodilator. This finding holds true regardless of whether the bronchodilator is given with or without exercise training.

In a prospective, randomized, placebo-controlled study, Weiner et al studied 30 patients with moderate to severe COPD. The study design was stepped: First, patients were assigned to six weeks of treatment with a long-acting bronchodilator or a placebo. During a second six-week period, the patients given the bronchodilator were randomized to additionally receive true exercise training or sham exercise training. During the final six-week period, the bronchodilator-plus-exercise training patients had another step added to their regimen: true inspiratory muscle training or sham inspiratory muscle training.

After the first six weeks, the actively treated patients experienced a small, statistically insignificant decrease in their mean Borg score, which assessed their perception of dyspnea. The addition of exercise training brought another drop in the mean Borg score, but the change remained statistically insignificant. However, a further decline in the mean Borg score followed inspiratory muscle training, and this decrease was significantly lower than not only the baseline measurement, but also the measurement obtained after exercise training.

Administration of a long-acting bronchodilator produced a statistically insignificant increase in forced expiratory volume in one second; neither exercise training nor inspiratory muscle training caused a further rise in this measurement.

Of the three treatments, exercise training had the greatest impact on the six-minute walk distance.

Weiner P, Magadle R, Berar-Yanay N, et al. The cumulative effect of long-acting bronchodilators, exercise, and inspiratory muscle training on the perception of dyspnea in patients with advanced COPD. Chest. 2000;118:672-678.

INHALED NO, BODY POSITION IN ARDS PATIENTS

Both prone positioning and inhaled nitric oxide (NO) administration improved oxygenation in patients with acute respiratory distress syndrome (ARDS), said the authors of a prospective study. Because the effects are independent of each other, the two strategies given together may produce better results than either method used alone.

Borelli et al analyzed the effects of prone positioning and inhaled NO, alone and combined, in 14 consecutive ARDS patients undergoing volume-controlled mechanical ventilation. Hemodynamic and gas exchange data were collected with the patients in four experimental conditions: supine or prone, with and without inhaled NO.

Both prone positioning and inhaled NO administration were associated with increases in arterial oxygen tension (32% and 44%, respectively), mixed venous partial oxygen pressure, and mixed venous hemoglobin oxygen saturation. Inhaled NO decreased venous admixture, mean pulmonary artery pressure, and pulmonary vascular resistance index.

No statistically significant interaction was found between the two treatments, which suggests that the effects of the two treatments are simply additive.

Eight patients benefited from prone positioning (both with and without inhaled NO); one additional patient responded to prone positioning only with inhaled NO. Ten patients responded to inhaled NO (in both the prone and supine positions), one patient responded to inhaled NO only when prone, and one responded to inhaled NO only in the supine position.

Overall, the average effect of prone positioning was the same with and without inhaled NO, and the average effect of inhaled NO was the same in both the prone and supine positions.

The authors suggest that if one treatment is found to increase oxygenation, application of the other may enhance the beneficial effect, because the effects of positioning and of inhaled NO are additive.

Borelli M, Lampati L, Vascotto E, et al. Hemodynamic and gas exchange response to inhaled nitric oxide and prone positioning in acute respiratory distress syndrome patients. Crit Care Med. 2000;28:2707-2712.

CONTINUOUS VERSUS INTERMITTENT ALBUTEROL NEBULIZATION

In patients with acute severe asthma, continuous and intermittent albuterol nebulization are equally effective, a new prospective, double-blind study suggests. Therefore, the choice of nebulization method rests upon logistical considerations, such as cost and nurse workload.

Of 42 consecutive patients who presented to an emergency department with an acute asthma exacerbation, 21 each were randomized to continuous or intermittent nebulization of albuterol (total dose, 27.5 mg) over six hours. At the end of the trial, patients who did not meet predetermined criteria were hospitalized. The primary outcome measurements were changes in spirometric values and clinical scores, which were based on a rating of 0 to 3 for each of five components: dyspnea, wheezing, accessory muscle contraction, respiratory rate, and pulsus paradoxus.

Both continuous and intermittent albuterol nebulization improved peak expiratory flow (PEF) and clinical severity scores. By the 40th minute, 38% of the continuous nebulization group and 33% of the intermittent group had 3-point reductions in clinical severity scores. At six hours, the two groups had achieved increases in PEF of 30% and 32%, respectively, and decreases in clinical severity scores of 6.3 and 6.1, respectively.

None of the differences between the two groups were significant; however, in both groups, the changes in PEF and clinical severity scores between baseline and six hours were significant.

A few patients did not respond to albuterol administration. Three patients in the continuous nebulization group and two in the intermittent group required admission to the intensive care unit. Overall, eight and nine patients, respectively, had to be hospitalized. No deaths or serious adverse effects were reported.

The authors suggest that an albuterol nebulization regimen of one dose every 20 minutes can be considered the equivalent of continuous nebulization.

Besbes-Ouanes L, Nouria S, Elatrous S, et al. Continuous versus intermittent nebulization of salbutamol in acute severe asthma: a randomized, controlled trial. Ann Emerg Med. 2000;36:198-203.

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