FLU VACCINE DOES NOT EXACERBATE ASTHMA

The influenza vaccine does not induce acute asthma exacerbations and should not be withheld from children with asthma, a large retrospective cohort analysis by Kramarz et al suggests. The researchers obtained computerized medical and vaccination records of children (age 1 to 6 years) from four large health maintenance organizations located on the West Coast of the United States. Data were available on 22,231 children during the 1993-1994 influenza season, 38,669 children during the 1994-1995 season, and 70,753 children during the 1995-1996 season.

After controlling for asthma severity, Kramarz et al found no increase in the incidence of acute asthma exacerbations within two days or two weeks of vaccination. In fact, during all three seasons, the researchers found a decrease in the incidence of asthma exacerbations during the two weeks after vaccination (as compared with that during other periods in the same group of children). This difference, although small each year, reached statistical significance in the 1993-1994 season. In addition, a separate analysis of children with severe asthma did not show an increased risk of exacerbations following vaccination.

"The results raise the question [of] whether influenza vaccination may cause a decrease in the incidence of asthma attacks beyond the two weeks (ie, vaccination may provide long-term protection against asthma exacerbations)," the researchers noted.

Kramarz P, DeStefano F, Gargiullo PM, et al. Does influenza vaccination exacerbate asthma? Analysis of a large cohort of children with asthma. Arch Fam Med. 2000;9:617-623.

GASTROESOPHAGEAL REFLUX: A CAUSE OF SINUSITIS?

Gastroesophageal reflux (GER) may contribute to the development of sinusitis in children, according to findings reported by Phipps et al. In this study, children with sinusitis refractory to medical treatment had a high prevalence of GER, and most improved following treatment for GER.

The researchers studied 30 consecutive children, age 2 to 18 years, who were referred for evaluation of chronic sinus disease. None of these patients responded to aggressive treatment with antibiotics or intranasal saline and nasal sprays. The researchers used 24-hour pH probes to evaluate the patients for GER and nasopharyngeal reflux. Patients with GER were treated with cisapride as well as a histamine2 blocker or proton pump inhibitor and diet modifications.

GER was found in 19 patients (63%). This prevalence is much higher than that expected in the general population (5%), according to Phipps et al. Six of the patients with GER (32%) also had nasopharyngeal reflux. Fifteen of the 19 patients with GER (79%) improved following treatment for that condition. One child's symptoms remained unchanged despite treatment for GER, another did not comply with treatment, and a third had not been given therapy for GER. Follow-up information was missing for the fourth child.

The researchers recommended that children with chronic sinus syndrome that is refractory to aggressive medical management should be evaluated for GER. The authors found the pH probes used in their study were safe and well tolerated.

Phipps CD, Wood WE, Gibson WS, Cochran WJ. Gastroesophageal reflux contributing to chronic sinus disease in children: a prospective analysis. Arch Otolaryngol Head Neck Surg. 2000;126:831-836.

IL-2 INCREASES CD4 CELL COUNTS

The addition of interleukin-2 (IL-2) therapy to antiretroviral therapy for patients infected with the human immunodeficiency virus (HIV) increases CD4 cell counts significantly more than does antiretroviral therapy alone, according to a recent study. The effects of IL-2 were dose-dependent.

The trial involved 78 HIV-infected patients who were already receiving antiretroviral therapy, had never taken IL-2, and had never developed an AIDS-associated condition. The patients were randomized to antiretroviral therapy alone or to antiretroviral therapy plus intermittent IL-2 therapy. Six cycles of IL-2 were given as 7.5 mIU every 12 hours for five days, every eight weeks. The dose was reduced in patients experiencing serious adverse effects.

After one year of treatment, the IL-2 group showed a significantly greater average increase in CD4 cell counts than did patients taking antiretroviral therapy alone (112% vs 18%). Patients who were able to tolerate higher doses of IL-2 had the greatest rise in CD4 cell counts (Figure 1).

Patients who received IL-2 also showed a small but significant decrease in viral load (mean change, -0.28 log10 copies), while patients given antiretroviral therapy alone had a slight increase in viral load. Viral suppression was achieved in a significantly greater proportion of the IL-2 group than in the group receiving antiretroviral therapy alone (67% vs 37%). "This is the first randomized controlled trial of IL-2 therapy demonstrating that IL-2 administered with potent [antiretroviral therapy] is associated with enhanced viral suppression," Davey et al noted.

Adverse effects associated with IL-2 included fever, fatigue, and myalgias. One patient developed thrombophlebitis, another had increased bilirubin levels, and a third had an acute exacerbation of mania. To avoid toxic effects, the researchers suggested that the IL-2 dosage may need to be adjusted in patients undergoing long-term therapy. "However," they concluded, "these toxic effects are largely predictable and do not diminish the rationale for selecting a starting dosage of proven efficacy in this range, especially since the CD4 cell response in this trial was strikingly dose-dependent."

Davey RT Jr, Murphy RL, Graziano FM, et al. Immunologic and virologic effects of subcutaneous interleukin-2 in combination with antiretroviral therapy: a randomized controlled trial. JAMA. 2000;284:183-189.

MINI-TRACHEOTOMY FOR SEVERE OBSTRUCTIVE SLEEP APNEA

A 2-mm tracheotomy, when combined with an airflow delivery device, is as effective as a large-tube tracheotomy in the treatment of severe obstructive sleep apnea. "Based on our clinical experience, we know that many people cannot use the [continuous positive airway pressure] mask but refuse to have a tracheotomy because they cannot stand the thought of having a big hole in their neck.… This study shows a new, potentially more tolerable approach," said lead author Alan Schwartz, MD.

The study involved five patients who had undergone large-tube tracheotomies. Caps were placed over the existing holes and a skinny tube was slipped through the cap to simulate a mini-tracheotomy. The patients were monitored for three nights.

The researchers found that a greater flow of air was needed to avoid apnea, so they administered high-flow transtracheal insufflation. However, the higher flow rate sometimes caused repetitive laryngeal obstructions and increased tracheal pressure as patients fell asleep. To avoid this problem, the researchers developed a computer-controlled flow delivery device that monitored tracheal pressure and varied the flow of air to keep this pressure below 20 cm H2O.

The high-flow system significantly lowered the frequency of obstructive apneas and hypopneas per hour (from 63.8 to 10.7). In addition, arousal frequency decreased from 67.5 to 0 per hour during rapid eye movement (REM) sleep and from 60.0 to 8.3 per hour during non-REM sleep with the new approach.

Schneider H, O'Hearn DJ, Leblanc K, et al. High-flow transtracheal insufflation treats obstructive sleep apnea: a pilot study. Am J Respir Crit Care Med. 2000;161:1869-1876.

DIESEL EXHAUST CAUSES AIRWAY INFLAMMATION

Inhalation of particulate matter in diesel exhaust causes an inflammatory response in the airways of healthy people, Nightingale et al found in a randomized, crossover study. "The study gives direct evidence of an important role for the particulate fraction of diesel exhaust in provoking this inflammatory response in human subjects," the researchers believe.

Three men and seven women with normal lung function and bronchial reactivity were studied after two hours of exposure to diesel exhaust particles (200 µg/m3 particulate matter of less than 10 µm aerodynamic diameter) or clean air. After a four-week washout period, the subjects were exposed to the other test condition.

Peak levels of exhaled carbon monoxide were significantly higher after the diesel exhaust exposure than after the clean air exposure (4.4 ppm vs 2.9 ppm). Diesel exhaust exposure was also associated with significant increases in neutrophils (41% vs 32%) and myeloperoxidase (151 ng/mL vs 115 ng/mL) in induced sputum.

Cardiovascular parameters, lung function, and concentrations of inflammatory markers in peripheral blood were similar under both test conditions. "Unlike those in previous studies, our subjects did not complain of any adverse effects of symptoms from the exposure to [diesel exhaust particulates]," Nightingale et al noted.

Nightingale JA, Maggs R, Cullinan P, et al. Airway inflammation after controlled exposure to diesel exhaust particulates. Am J Respir Crit Care Med. 2000;162:161-166.

PREDICTORS OF NEAR-FATAL AND FATAL ASTHMA

Nearly half of near-fatal and fatal asthma attacks occur suddenly and unexpectedly, outside of the hospital, and in stable, young, atopic patients who used corticosteroids on a daily basis. These findings are based on survey responses from 400 asthma specialists who submitted information on 25 cases of near-fatal asthma and 20 cases of fatal asthma.

Among patients with near-fatal asthma, the mean age at the time of the episode was 29.4 years. The event occurred suddenly (ie, in less than three hours) in 60% of cases. All of the patients had been using short-acting inhaled ß-agonists, and 88% had been taking inhaled corticosteroids on a daily basis. Compliance with these therapies was rated as good to excellent in 60% of patients.

Precipitating factors for near-fatal asthma included overuse of inhaled ß-agonists in six patients and a delay in initiation of oral corticosteroids in five patients. In the 20 patients with fatal asthma, the mean age at the time of death was 21.7 years. All of the patients had been using short-acting inhaled ß-agonists, 80% had been taking inhaled corticosteroids on a daily basis, and 30% had also been using oral corticosteroids. Sixty percent of the patients were believed to have good to excellent compliance with corticosteroid therapy.

Precipitating factors of fatal asthma included overuse of inhaled ß-agonists in nine patients and a delay in initiating oral corticosteroids in four patients. Risk factors for fatal asthma included exercising in cold weather, over-reliance on home nebulizers, inadvertently ingesting nuts or peanuts, and a delay in seeking medical care on holiday weekends.

Predisposing psychosocial factors were noted in 44% of patients with near-fatal asthma and 45% of those who died from asthma. These factors included self-denial and/or poor care, depression, drug abuse, and loss of a loved one.

Hannaway PJ. Demographic characteristics of patients experiencing near-fatal and fatal asthma: results of a regional survey of 400 asthma specialists. Ann Allergy Asthma Immunol. 2000;84:587-593.

SHORTER DURATION OF TREATMENT FOR ACETAMINOPHEN OVERDOSE

A short course of oral acetylcysteine therapy appears to be safe and effective for patients who do not show evidence of hepatotoxicity within 36 hours of an acute acetaminophen overdose, according to the results of a recent retrospective study conducted by Woo et al.

Acetylcysteine enhances detoxification of the reactive metabolite of acetaminophen; however, in most cases, the parent compound of this drug is eliminated completely within 10 to 20 hours, and further production of the reactive metabolite is unlikely. Based on this information, Woo et al hypothesized that treatment with acetylcysteine is probably not needed after 20 hours.

The researchers reviewed the medical records of 75 patients with possible or probable toxicity following an acute overdose of acetaminophen. A third of the group had been treated with acetylcysteine for less than 24 hours, a third for 24 to 36 hours, and a third for 37 to 64 hours. In all patients, therapy had been initiated within 24 hours of acetaminophen ingestion.

The incidence of hepatotoxicity (ie, aminotransferase levels above 1,000 IU/L) is shown in Table 1. None of the patients died or required liver transplantation.

"Our experience and that of others suggests that evidence of impending hepatotoxicity is apparent within 30 to 36 hours after an acute ingestion," according to the researchers. Because of these data, they believe that patients without such evidence within 36 hours can be safely treated with acetylcysteine for 24 hours or less.

Woo O, Mueller PD, Olson KR, et al. Shorter duration of oral N-acetylcysteine therapy for acute acetaminophen overdose. Ann Emerg Med. 2000;35:363-368.

OCCUPATIONAL ASTHMA AND HOSPITALIZATION RISK

Workers with occupational asthma are at higher risk for hospitalization than are those with musculoskeletal injury, new findings suggest. "Given that [occupational asthma] is preventable and that serious sequelae may develop, our findings underscore the need for greater attention directed toward primary prevention of this condition," according to Liss et al.

The researchers studied 844 workers with occupational asthma, 1,556 workers with musculoskeletal injury, and 402 asthma patients who attended an asthma clinic. The most common causes of occupational asthma were exposure to isocyanates (52%), flour (6%), and metals (4%). Other allergens included grains, plastics, non-cedar wood dust, welding fumes, paint, chlorine, and solvents.

The rate of hospitalizations for all causes was 47% for the asthma clinic patients, 39.2% for the occupational asthma patients, and 29.2% for the musculoskeletal injury group. Compared with the latter group, subjects with occupational asthma were significantly more likely to be hospitalized for all causes; most of this difference was attributable to the markedly higher rates of hospitalization for respiratory diseases and asthma in the occupational asthma group.

Occupational asthma patients were about half as likely as asthma clinic patients to be hospitalized for asthma and respiratory disease but were 30% more likely than asthma clinic patients to be admitted for ischemic heart disease. Factors associated with hospitalization for asthma in the occupational asthma group included exposure to agents other than isocyanate, nonsmoking status, and older age.

Interestingly, the risk of hospitalization for respiratory diseases declined markedly five or more years after the onset of symptoms in patients with occupational asthma. Liss et al believe that the effect of work-related sensitization might decline following diagnosis and removal of the causative agent.

Liss GM, Tarlo SM, MacFarlane Y, Yeung KS. Hospitalization among workers compensated for occupational asthma. Am J Respir Crit Care Med. 2000;162:112-118.