ASTHMA ASSOCIATED WITH LOWER RESPIRATORY SYMPTOMS

Asthma exacerbations are often associated with upper respiratory infections (URIs), more than half of which are caused by rhinoviruses. A longitudinal cohort study by Corne et al has found that people with asthma are not at greater risk of rhinovirus infections; however, they do have more frequent lower respiratory infections (LRIs) caused by rhinoviruses, and resulting symptoms are more severe and longer-lasting.

Seventy-six adult, cohabiting couples, each with one person having atopic asthma and one with no symptoms, were enrolled. For three months, participants recorded peak expiratory flow (PEF) twice daily and kept a diary of respiratory symptoms. Participants also visited the hospital every two weeks, where nasal aspirates were taken and analyzed for rhinovirus.

Fifty-one participants developed one or more rhinovirus infections during the study. Thirty-eight of 378 samples (10%) from the asthma group tested positive for rhinovirus, as did 32 of 375 samples (9%) from the non-asthma group. Risk of rhinovirus infection did not differ between groups, nor did severity or duration of URI symptoms.

In contrast, LRIs were more likely to be associated with rhinoviruses in the asthma group than in the non-asthma group. Furthermore, the severity and duration of symptoms in those with LRI were significantly greater in the asthma group, as was the mean decrease in peak expiratory flow (14.1% vs 9.5% in those without asthma).

Corne JM, Marshall C, Smith S, et al. Frequency, severity, and duration of rhinovirus infections in asthmatic and non-asthmatic individuals: a longitudinal cohort study. Lancet. 2002;359:831-834.

IMPROVED BRONCHODILATOR RESPONSE WITH MUCUS CLEARANCE

The mucus clearance device (MCD) contains a steel ball that produces oscillations in air pressure and flow, which loosen and help clear mucus. In a study of patients with chronic obstructive pulmonary disease (COPD), Wolkove et al found that using the MCD before inhaled bronchodilation can enhance response to the drug.

Twenty-three patients with COPD were evaluated on three separate days. On day 1, they were given either the actual or a sham MCD and taught how to use it. On days 2 and 3, pulmonary function tests were performed before and after 10 minutes of MCD use. All patients then took four puffs of a bronchodilator, each puff delivering 20 µg ipratropium bromide and 120 µg albuterol. Pulmonary function tests were repeated 30, 60, and 120 minutes thereafter.

The mean improvement from baseline in forced expiratory volume in one second (FEV1) at 120 minutes after bronchodilator use was 186 mL in the MCD group, compared with 130 mL in the sham group. When expressed as a percentage change from baseline, the improvement in lung function was greater in the MCD group at all time points, but the difference in magnitude of improvement in FEV1 between groups was not significant until 120 minutes. The investigators concluded that using the MCD may improve both treatment response and pulmonary function in patients with COPD.

Wolkove N, Kamel H, Rotaple M, Baltzan MA Jr. Use of a mucus clearance device enhances the bronchodilator response in patients with stable COPD. Chest. 2002;121:702-707.

DELAYED ANTIBIOTIC PRESCRIPTIONS FOR THE COMMON COLD

Antibiotics are often used to treat the common cold, despite evidence showing their inefficacy. A single-blind, controlled study by Arroll et al has shown that having patients wait three days before filling their prescriptions resulted in reduced antibiotic use for the common cold without compromising patient safety or comfort.

One hundred twenty-nine patients with upper respiratory symptoms were enrolled by 15 family physicians. Patients were given a prescription for antibiotics with instructions either to fill it after three days if their symptoms did not improve or to begin treatment immediately. Patients were given daily symptom checklists to complete for 10 days. They also recorded their temperatures daily and noted whether they had nasal congestion, the color of mucus and sputum, and time of day coughing was most frequent. Patients were contacted on days 3, 7, and 10 and asked about their body temperature and symptoms.

Patients in the delayed-use group were less likely to use antibiotics (48%) than those in the immediate-use group (85%).

Although delayed prescription use reduced total antibiotic use, the investigators noted that 48% was still a high proportion for an illness in which antibiotics are usually not effective. The authors suggested that family physicians not prescribe antibiotics for the common cold.

Arroll B, Kenealy T, Kerse N. Do delayed prescriptions reduce the use of antibiotics for the common cold? A single-blind controlled trial. J Fam Pract. 2002;51:324-328.

HERBAL FORMULATION EFFECTIVE IN ALLERGIC RHINITIS

Although herbal therapies have been used for allergic rhinitis (AR), none have been studied using clinical trials. Hu et al conducted a randomized, double-blind trial to determine the efficacy of biminne, a formulation of 11 traditional Chinese herbs, in patients with perennial AR.

Fifty patients completed the study. All patients received symptom and adverse-event diaries and capsules every four weeks for 12 weeks. Patients took five capsules twice daily; the capsules contained biminne or placebo. At each visit, blood samples were taken and diaries collected. At the final visit, clinical and physical examinations were performed. Serum immunoglobulin E (IgE) levels were measured before and after the trial. Patients completed a quality-of-life questionnaire and symptom assessment. Follow-up information was obtained after one year.

Compared with the placebo cohort, the biminne group had a greater decrease in symptom severity, greater improvement in quality-of-life scores, and significantly more improvement was noted during the physician’s overall examination. Sneezing, in particular, was reduced. IgE levels were decreased in the biminne group but were unchanged in the placebo group. After one year, the benefits of biminne treatment were partly maintained.

In a dose-response study that included 22 patients from the original placebo group, both half- and full-strength doses of biminne were effective. The authors concluded that biminne is safe and effective for treating AR symptoms.

Hu G, Walls RS, Bass D, et al. The Chinese herbal formulation biminne in management of perennial allergic rhinitis: a randomized, double-blind, placebo-controlled, 12-week clinical trial. Ann Allergy Asthma Immunol. 2002;88:478-487.

PATIENTS ALTER BREATHING PATTERNS TO MINIMIZE DYSPNEA

Little research has been done on how variations in breathing contribute to the clinical manifestation of lung disease. A recent study by Brack et al has found that patients with restrictive lung disease have the ability to achieve different tidal volumes but may deliberately choose a breathing pattern that lessens dyspnea.

Ten men with restrictive lung disease and a control group of seven healthy, age-matched men took part in the study. Each subject’s normal ventilation was measured for one hour, after which mean tidal volume and respiratory cycle time were calculated. A computer was then used to help the subjects breathe at nine different tidal volumes for five minutes each. After each five-minute test, dyspnea was measured by asking, “How uncomfortable is your breathing?” The relationship between variations in tidal volume and dyspnea was calculated.

Compared with the control group, patients with restrictive lung disease had only slight variations in normal breathing. For example, they showed decreases in the coefficients of variation of 56%, 46%, and 33% for tidal volume, expiratory time, and inspiratory time, respectively.

The patients were able to reproduce the nine tidal volumes with the same degree of accuracy as the control group, but they experienced dyspnea after only slight variations in tidal volume. This observation led the authors to conclude that patients with restrictive lung disease deliberately breathe with little variation to avoid dyspnea.

Brack T, Jubran A, Tobin MJ. Dyspnea and decreased variability of breathing in patients with restrictive lung disease. Am J Respir Crit Care Med. 2002;165:1260-1264.

SLEEP-DISORDERED BREATHING IN THE ELDERLY

Several population-based studies have shown a relationship between sleep-disordered breathing (SDB), obesity, and snoring. However, because SDB is largely undiagnosed, information on demographic patterns and predictive factors in the general population is limited. To investigate the association of sex, age, snoring, and obesity with SDB, Young et al used data from the Sleep Heart Health Study, a multicenter study of SDB and cardiovascular disease.

Complete data were available for 5,615 community-dwelling adults ranging in age from 40 to 98 years. Not surprisingly, male sex, advancing age, and snoring were linked to an increased risk of SDB; however, some unexpected findings did emerge when patients were stratified by age: The association of body mass index (see Figure 1), neck circumference, and waist-to-hip ratio with SDB all decreased with advancing age and became statistically insignificant by age 80 years. Similarly, the relationship between breathing pauses and SDB decreased as age increased.

Young et al did not detect a large increase in the incidence of SDB in people older than 60 years. The investigators acknowledged that this finding is inconsistent with the results of several other studies, but they noted that the Sleep Heart Health Study had several potential sources of bias that could have resulted in the overestimating or underestimating of SDB according to age-group.

In older people, SDB was poorly predicted by high body mass index, neck circumference, waist-to-hip ratio, and self-reported breathing pauses, indicating that SDB in older people would be missed if these criteria alone were used. The authors conclude that SDB in the elderly is a condition distinct from SDB in younger people and needs further research.

Young T, Shahar E, Nieto FJ, et al. Predictors of sleep-disordered breathing in community-dwelling adults: the Sleep Heart Health Study. Arch Intern Med. 2002;162:893-900.

Figure 1 Effect of Age and Physique on an Apnea-Hypopnea Index of 15 or Greater

Logarithmic scale of odds ratios for an apnea-hypopnea index of 15 or greater estimated for an increase of one standard deviation in body mass index. The ratio declines as age progresses. Error bars indicate 95% confidence interval. Adapted from Young et al. Arch Intern Med. 2002.

MECHANICAL VENTILATION REDUCES DIAPHRAGM INJURY

Mechanical ventilation (MV) may protect the diaphragm from damage during sepsis. A study of endotoxin’s effects on rats has demonstrated that MV maintains sarcolemmal integrity and improves diaphragm force production during endotoxemia.

Ebihara et al placed pathogen-free adult male Sprague-Dawley rats into three groups: a control group comprising spontaneously breathing animals, a spontaneously breathing group in which Escherichia coli lipopolysaccharide (LPS) injection was used to induce endotoxemia, and a group receiving both LPS and MV.

The researchers later excised the rats’ diaphragms and examined cell integrity using a low-molecular-weight tracer dye that could not penetrate the cytoplasm of myofibers with intact sarcolemma. The control animals showed no sign of dye uptake. In contrast, the spontaneously breathing LPS group showed cytoplasmic staining of varying degrees; the extent of this staining was significantly reduced in the LPS plus MV group.

Levels of nitric oxide and protein carbonyls, both markers of oxidative stress, were markedly higher in the two LPS groups than in the controls. This indicated that MV’s protective effects were not related to inhibition of oxidation. Investigators speculated that MV may have reduced diaphragm blood flow during endotoxemic shock or lowered the mechanical load placed on endotoxemia-weakened sarcolemma.

Ebihara S, Hussain SNA, Danialou G, et al. Mechanical ventilation protects against diaphragm injury in sepsis. Am J Respir Crit Care Med. 2002;165: 221-228.