LITERATURE MONITOR:
A REVIEW OF RECENTLY PUBLISHED
CLINICAL ARTICLES

COAGULATION FACTOR XI: A RISK FACTOR FOR VENOUS THROMBOSIS

The risk of deep venous thrombosis is more than twice as high in patients with high levels of coagulation factor XI than in patients with normal levels. Because 10% of the population has high factor XI levels, Meijers et al believe that this variable is "an important contributor to the overall burden of venous thrombosis."

These researchers determined the factor XI antigen levels in 474 patients with a first episode of deep venous thrombosis and 474 controls enrolled in the Leiden Thrombophilia Study. Meijers et al found a dose-response relationship between factor XI levels and the risk for deep venous thrombosis. This association remained significant even after the researchers controlled for oral-contraceptive use, sex, age, and genetic risk factors. Subjects who had factor XI levels above the 90th percentile had an odds ratio for deep venous thrombosis of 2.2, compared with patients who had levels at or below the 90th percentile.

The findings also suggest that 11% of all cases of thrombosis may be attributable to high factor XI levels. "We postulate that a high level of factor XI causes thrombosis through sustained generation of thrombin, which leads to the protection of fibrin from proteolysis," Meijers et al reported.

Meijers JC, Tekelenburg WLH, Bouma BN, et al. High levels of coagulation factor XI as a risk factor for venous thrombosis. N Engl J Med. 2000;342:696-701.

DIAGNOSING OBSTRUCTIVE AIRWAY DISEASE

The individual signs and symptoms of obstructive airway disease (OAD) have little diagnostic value, results from a recent study suggest. Instead, Straus et al found that a combination of four signs/symptoms--self-reported history of chronic OAD, a smoking history of greater than 40 pack-years, age 45 years or older, and maximum laryngeal height of 4 cm or less--are predictive of OAD.

The researchers noted that spirometry should always be included in the workup (if readily available) because it can definitively establish a diagnosis of airway obstruction and provide prognostic information. "However, in those settings in which spirometry is unavailable, our model provides useful diagnostic support for the clinician," they concluded.

Straus et al evaluated the accuracy of the following elements of the clinical examination in diagnosing OAD: patient self-reported history of chronic OAD, smoking history, wheezing on auscultation, laryngeal height, and laryngeal descent. A total of 76 patients with known chronic OAD, 114 patients with suspected OAD, and 119 patients without known or suspected OAD underwent clinical examination and spirometry. The gold standard for the diagnosis of OAD was a forced expiratory volume in one second (FEV1) and a ratio of FEV1 to forced vital capacity both below the fifth percentile.

The only factors that were significantly associated with OAD diagnosis were a smoking history of more than 40 pack-years, a self-reported history of chronic OAD, maximum laryngeal height of at least 4 cm, and age 45 years or older. Patients with all four of these characteristics had a likelihood ratio for OAD of 220.5, whereas patients with none of them had a likelihood ratio of 0.13.

Straus SE, McAlister FA, Sackett DL, Deeks JJ. The accuracy of patient history, wheezing, and laryngeal measurements in diagnosing obstructive airway disease. JAMA. 2000;283:1853-1857.

REDUCING COLDS AMONG CHILDREN IN DAY CARE

A simple infection control technique significantly reduced the transmission of colds among children age 2 years and younger who attended day care, according to a recent study by Roberts et al.

Eleven day care centers in an Australian city were assigned to an infection control intervention; 12 others served as control centers. The parents of 558 children were asked to report symptoms of illness every two weeks for nine months; 299 of these children attended the intervention centers, and the other 259 were enrolled at the control centers.

At the intervention centers, the staff was educated about transmission of infection and taught a hand-washing technique (ie, wash for 10 seconds and rinse for 10 seconds). The staff was also asked to teach this technique to the children and to wash the hands of children too young to do so unassisted. The staff and children were told to wash their hands after using the bathroom, before eating, after a diaper change, and after wiping a nose (unless a small plastic bag had been used to cover the hand like a glove while the nose was wiped).

Overall, the two groups of children had a similar number of colds. However, the intervention had a significant effect on children age 2 years and younger--the number of colds was reduced by 11% to 17% in centers that had high compliance with the recommended practices.

The intervention may have had an effect only on the younger children because they are least able to blow their own noses and wash their own hands. It is also possible the intervention only worked in younger children because they are less mobile and have less contact with playmates than do older children.

This reduction in colds did not translate into a significant reduction in days absent from day care, however. As Roberts et al explained, "this is consistent with practice in Australia where children with upper respiratory infection are rarely kept away from care."

Roberts L, Smith W, Jorm L, et al. Effect of infection control measures on the frequency of upper respiratory infection in child care: a randomized, controlled trial. Pediatrics. 2000;105:738-742.

INCENTIVE SPIROMETRY: NOT USEFUL AFTER THORACIC SURGERY

Routine use of incentive spirometry appears to be ineffective in preventing postoperative pulmonary complications after thoracic surgery, according to new findings.

Gosselink et al randomized 67 patients undergoing elective thoracic surgery for lung or esophagus resection to physiotherapy alone or physiotherapy plus incentive spirometry. Both groups were instructed to perform the following each hour after surgery: two series of five to 10 slow maximal inspiratory maneuvers with breath-holding, followed by forced expirations and coughing. The only difference was that the spirometry group performed the maximal inspiratory maneuvers with a volume feedback incentive spirometer.

In both groups, pulmonary function declined significantly after surgery and improved significantly by day 21. This recovery of pulmonary function was similar between the two groups.

The rate of pulmonary complications was relatively low in this study and was similar between the two groups (about 12% in each). The groups also had similar mean values for hospital and intensive care unit stays, white blood cell count, chest radiograph score, body temperature, and number of bronchoscopies.

The findings are in accordance with previous studies involving patients who underwent abdominal or cardiac surgery. "Although we cannot rule out beneficial effects in a subgroup of high-risk patients, routine use of [incentive spirometry] after thoracic surgery seems to be ineffective," Gosselink et al concluded.

Gosselink R, Schrever K, Cops P, et al. Incentive spirometry does not enhance recovery after thoracic surgery. Crit Care Med. 2000;28:679-683.

BRONCHIAL REACTIVITY IN CROHN'S DISEASE

Bronchial hyperresponsiveness is common in children and adolescents with Crohn's disease, even in those without evidence of respiratory problems, according to findings from a recent study. The data suggest that bronchial hyperresponsiveness "is likely to be the expression of subclinical airway inflammation," reported Mansi et al.

The researchers measured forced expiratory volume in one second (FEV1) in 14 patients with Crohn's disease, 10 patients with mild bronchial asthma, and 10 healthy nonatopic subjects. Subjects with an FEV1 above 80% of the predicted value underwent a methacholine challenge.

Bronchial hyperresponsiveness was found in 10 of the 14 patients with Crohn's disease (71%). Seven of these hyperresponsive patients were nonatopic. Hyperresponsiveness was also found in all of the asthma patients but in none of the control subjects.

Interestingly, the hyperreactive patients with Crohn's disease showed no signs or symptoms of respiratory problems. This finding "supports the supposition of subclinical airway involvement," noted Mansi et al.

Bronchial responsiveness was reevaluated in five patients with Crohn's disease a median of 25 months after the first test. The results showed a significant decrease in bronchial hyperreactivity over time. This decrease was not related to disease status or treatment.

Mansi A, Cucchiara S, Greco L, et al. Bronchial hyperresponsiveness in children and adolescents with Crohn's disease. Am J Respir Crit Care Med. 2000;161:1051-1054.

LEUKOTRIENE ANTAGONISTS AND CHURG-STRAUSS SYNDROME

Do leukotriene antagonists cause--or contribute to the onset of--Churg-Strauss syndrome in asthma patients? New evidence suggests that the answer is "no"; rather, these drugs seem to unmask an underlying systemic eosinophilic disorder that initially may have been characterized as moderate to severe asthma.

Wechsler et al came to this conclusion after examining four cases of Churg-Strauss syndrome in asthma patients (one man and three women) who were taking montelukast. In each case, the patient had a history of multiple asthma exacerbations requiring frequent courses of oral systemic corticosteroids or high doses of inhaled corticosteroids. At the time Churg-Strauss syndrome became manifest in each patient, the corticosteroid dose was being tapered.

These authors had previously reported eight cases in which Churg-Strauss developed in asthma patients being treated with zafirlukast. However, they have also found two cases in which the syndrome arose in patients given inhaled corticosteroids and salmeterol, but not a leukotriene antagonist. In all these cases, the common factor was a reduction in the corticosteroid dosage.

Wechsler et al concluded, therefore, that "the high-dose inhaled corticosteroids used in these patients, in conjunction with intermittent systemic corticosteroid treatment, had suppressed manifestations of systemic eosinophilia." The association with leukotriene antagonists appears to be coincidental, not causal, they suggested. The authors conceded the possibility that an allergic response to montelukast or zafirlukast may have played a role in some cases, although they consider this unlikely, given that the two drugs have distinctly different molecular structures. Thus, the controversy concerning this issue will continue.

Wechsler ME, Finn D, Gunawardena D, et al. Churg-Strauss syndrome in patients receiving montelukast as treatment for asthma. Chest. 2000;117:708-713.

PREDISPOSING RISK FACTORS FOR ASTHMA EXACERBATIONS

Total immunoglobulin E (IgE) and sensitization to inhalant allergens are predisposing risk factors for asthma exacerbations among young children, according to new findings reported by Wever-Hess et al. The results also showed that children living in damp houses are at increased risk for recurrences.

A total of 257 children younger than age 5 years were followed for two years. An asthma exacerbation was defined as an increase in cough, wheeze, and/or breathlessness; an increase in ß 2-agonist use; and a need for short-course oral corticosteroids.

During follow-up, at least one exacerbation occurred in 63% of children age 1 year and younger and in 40% of children age 2 to 4 years. Recurrent exacerbations were found in 18% and 15% of the respective subgroups.

Among the children age 1 year and younger, damp housing and colds were predisposing risk factors for exacerbation (odds ratios [OR], 7.6 and 3.6, respectively) and sensitization to inhalant allergens and damp housing were predisposing risk factors for recurrent exacerbations (ORs, 8.1 and 3.8, respectively). Hospital admissions were significantly associated with the number of exacerbations.

Among children age 2 to 4 years, mean age at initial presentation and total IgE level were predisposing risk factors for exacerbation (ORs, 0.92 and 2.3, respectively). There were no predisposing risk factors for recurrent exacerbations in this group. Hospital admissions were significantly associated with damp housing, according to Wever-Hess et al.

Wever-Hess J, Kouwenberg JM, Duiverman EJ, et al. Risk factors for exacerbations and hospital admissions in asthma of early childhood. Pediatr Pulmonol. 2000;29:250-256.

ALLERGY CLINICS BENEFIT INNER-CITY ASTHMA PATIENTS

Inner-city asthma patients required fewer hospitalizations and emergency department (ED) visits and showed significant improvement in disease severity when treated in an allergy clinic instead of by primary care or ED physicians.

Vilar et al reviewed the medical records of 100 asthma patients treated at an allergy clinic for two consecutive years. The researchers compared the frequency of hospitalizations, ED visits, and asthma severity during the year before the patients began attending the allergy clinic and in the first and second years of treatment at the clinic.

The intervention included clinic visits every one to eight weeks, peak flow meter training and home monitoring, instruction on use of metered-dose inhalers and spacers, and optimal anti-inflammatory and bronchodilator dosages. In addition, the patients were taught about environmental control measures and received immunotherapy when indicated.

The frequency of hospitalizations and ED visits significantly declined over time once the patients began attending the clinic; the greatest decrease occurred during the first year of clinic treatment. Disease severity also significantly declined over time; not surprisingly, the greatest reduction was found among compliant patients.

In the second phase of the study, 23 patients from the allergy clinic and 21 patients treated by primary care or ED physicians completed a quality-of-life survey. Overall, scores were higher among patients treated in the allergy clinic than among those who received standard care; the only significant differences were found among answers focusing on mental health and social functioning.

Vilar MEB, Reddy BM, Silverman BA, et al. Superior clinical outcomes of inner city asthma patients treated in an allergy clinic. Ann Allergy Asthma Immunol. 2000;84:299-303.

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