A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults.

BACKGROUND: The incidence and severity of herpes zoster and postherpetic neuralgia increase with age in association with a progressive decline in cell-mediated immunity to varicella-zoster virus (VZV). We tested the hypothesis that vaccination against VZV would decrease the incidence, severity, or both of herpes zoster and postherpetic neuralgia among older adults. METHODS: We enrolled 38,546 adults 60 years of age or older in a randomized, double-blind, placebo-controlled trial of an investigational live attenuated Oka/Merck VZV vaccine ("zoster vaccine"). Herpes zoster was diagnosed according to clinical and laboratory criteria. The pain and discomfort associated with herpes zoster were measured repeatedly for six months. The primary end point was the burden of illness due to herpes zoster, a measure affected by the incidence, severity, and duration of the associated pain and discomfort. The secondary end point was the incidence of postherpetic neuralgia. RESULTS: More than 95 percent of the subjects continued in the study to its completion, with a median of 3.12 years of surveillance for herpes zoster. A total of 957 confirmed cases of herpes zoster (315 among vaccine recipients and 642 among placebo recipients) and 107 cases of postherpetic neuralgia (27 among vaccine recipients and 80 among placebo recipients) were included in the efficacy analysis. The use of the zoster vaccine reduced the burden of illness due to herpes zoster by 61.1 percent (P<0.001), reduced the incidence of postherpetic neuralgia by 66.5 percent (P<0.001), and reduced the incidence of herpes zoster by 51.3 percent (P<0.001). Reactions at the injection site were more frequent among vaccine recipients but were generally mild. CONCLUSIONS: The zoster vaccine markedly reduced morbidity from herpes zoster and postherpetic neuralgia among older adults.

Determinants of accrual of women to a large, multicenter clinical trials program of human immunodeficiency virus infection. The AIDS Clinical Trials Group.

To determine factors influencing the enrollment of women in a large multicenter human immunodeficiency virus (HIV) clinical trials program in the United States, we analyzed enrollment and demographic data of the AIDS Clinical Trials Group (ACTG) during the period 1987-90. Women comprised 6.7% of 11,909 ACTG participants enrolled in 1987-90. Women entering ACTG trials were significantly more likely to be white (48.5%) and less likely to have ever used i.v. drugs (22.6%) than U.S. women reported to have AIDS (26.5% were white; 51.0% had ever used i.v. drugs, p < 0.0001). In a multiple logistic regression model, specific attributes of individual trials did not influence enrollment of women with the exception that trials that targeted asymptomatic persons had greater enrollment of women. There was wide variation among research units in the percentage of women enrolled (1.0-37.5%), and evidence of significant regional variation in the ability of units to recruit available women. Units with female principal or coprincipal investigators had more than twice the percentage of female enrollment as units headed by men (10.8 vs. 5.3%, p < 0.001). Enrollment of women in a large HIV clinical trials program was low and appeared to be influenced more by demographic and geographic factors that attributes of specific trials. An apparent positive influence of female leadership on the enrollment of women warrants further study.

Prevalence and patterns of use of concomitant medications among participants in three multicenter human immunodeficiency virus type I clinical trials. AIDS Clinical Trials Group (ACTG).

Data on the prevalence and patterns of use of concomitant medications among participants in three large phase III clinical trials of zidovudine (ZDV) in human immunodeficiency virus type 1 (HIV-1) infection were analyzed. Overall, 2,801 patients reported 43,331 uses of concomitant medications. Over 85% of clinical trial participants used one or more concomitant medications at some point during the study. Patients with acquired immune deficiency syndrome (AIDS) used an average of 7.1 drugs per month. Patients with AIDS-related complex (ARC) or who were asymptomatic used relatively fewer drugs: 3.1 and 2.7 per month, respectively. Fourteen percent of patients with AIDS used more than 10 concomitant medications per month. The three most commonly utilized classes of drugs were antiinfectives (57%), analgesics or antipyretics (55%), and vitamins (47%). A total of 17% of patients overall and 30% of AIDS patients used acyclovir while on trial. Consumption of prescription drugs was greater, and "over-the-counter" drugs less, among AIDS patients. Reported use of agents not approved by the Food and Drug Administration or approved drugs used for off-label indications was infrequent. Overall use of concomitant medications did not differ across demographic subgroups when corrected for disease stage at the time of enrollment. White, non-Hispanic, homosexual and bisexual men consumed significantly more antivirals and vitamins than other trial participants. Women in all three protocols took more analgesics or antipyretics than did men.(ABSTRACT TRUNCATED AT 250 WORDS)

Primary prophylaxis for Pneumocystis carinii pneumonia in HIV-infected people with CD4 counts below 200/mm3: a cost-effectiveness analysis.

We developed a decision-analytic model to assess the effectiveness and costs of dapsone, trimethoprim-sulfamethoxazole, or aerosolized pentamidine as initial prophylaxis for Pneumocystis carinii pneumonia in human immunodeficiency virus-infected people without prior symptoms AIDS and with CD4 counts less than 200/mm3. Each strategy increased life expectancy by about 18% compared with no prophylaxis; annual per-person costs were $440, $700, and $1,680 for dapsone, trimethoprim-sulfamethoxazole, and aerosolized pentamidine, respectively. These cost differences make a strategy beginning with dapsone most cost effective, with an incremental cost-effectiveness ratio of $13,400 per life year saved compared with no prophylaxis. Aerosolized pentamidine was substantially less cost effective, but the incremental cost effectiveness ratios were highly dependent on estimates for quality of life, efficacy, toxicity, and compliance. We conclude that, based on currently available data, initial prophylaxis with either dapsone or trimethoprim-sulfamethoxazole is most cost effective. For every 100,000 people treated, starting prophylaxis with trimethoprim-sulfamethoxazole or dapsone--with crossover to aerosolized pentamidine if oral therapy is not tolerated--may save between $98 million and $124 million per year.

Increased bronchial reactivity to inhaled histamine in nonsmoking grain workers with normal lung function.

We measured nonspecific bronchial reactivity to inhaled histamine in 26 lifetime nonsmoking grain handlers and 29 lifetime nonsmoking unexposed control subjects matched for age, sex and specific conductance. Routine lung function tests revealed a total lung capacity that was higher in control subjects than in workers (P less than 0.05) with no difference in other subdivisions of lung volume, or expiratory flow rates between the two groups. An index of allergy was significantly greater in the control subjects than in the grain workers (P less than 0.01). None of the grain handlers was sensitive to grain dust by history or by skin tests. Respiratory symptoms (cough, sputum, dyspnea, or wheezing) were more prevalent in the grain workers than in controls (P less than 0.05). The mean concentration of histamine required to reduce the specific conductance by 35 percent was 4.5 +/- 2.0 mg/ml in grain workers and 5.9 +/- 3.0 mg/ml in controls (P less than 0.05). Chronic exposure to grain dust in nonallergic individuals appears to be associated with both increased prevalence of respiratory symptoms and increased nonspecific bronchial reactivity when compared to nonexposed control subjects.

Pulmonary function in Pi M and MZ grainworkers.

Twenty-eight men with the Pi MZ phenotype who have been employed in the Saskatchewan country grain elevators and thus regularly exposed to high levels of grain dust, were case matched for age, years of employment, employment status, smoking status, and smoking history with grainworkers of type Pi M. Individuals answered a questionnaire, had a chest roentgenogram, skin tests, and performed a battery of pulmonary function tests. There were no differences between the two groups in prevalence of symptoms or atopy. Although not statistically significant, the MZ group had three times as many individuals with abnormal roentgenograms suggestive of COPD as the M group. The Pi MZ grainworkers had consistently poorer mean results for the pulmonary function tests with significantly lower mean values for FEV1, FEV1/FVC, MMFR, and Vmax50, leading us to suggest that Pi MZ individuals may be at higher risk of COPD than Pi M individuals, but only in the presence of other risk factors such as grain dust exposure.

Reduction of the single breath CO diffusing capacity in cystic fibrosis.

The single breath diffusing capacity of the lung for carbon monoxide (Dsb) was measured using three equations to describe CO uptake separately during inhalation, breath holding, and exhalation in 24 patients with cystic fibrosis and 30 control subjects with similar age and height distributions. Using the control group, we developed two prediction equations for Dsb: one based on height, age, and sex; and another based on alveolar lung volume (VA) to the 2/3 power. We also developed a prediction for Dsb/VA (Kco) based on height. The Dsb as percent predicted (% pred) using either prediction equation decreased with increasing age and height as well as with decreasing % pred maximal midexpiratory flow rate (FEF25-75) in cystic fibrosis patients but not in controls. The Kco (% pred) also decreased in cystic fibrosis with increasing age and decreasing percent pred FEF25-75. We conclude that in patients with cystic fibrosis, Dsb decreases with variables that relate to increasing disease severity (age, height, and increasing airflow obstruction).

Relationship between bronchial response to respiratory heat exchange and nonspecific airways reactivity in asthmatic patients.

In this study we have examined the relationship between the bronchial response to inhaled histamine and the bronchial response to breathing cold air at rest in nine control subjects and nine patients with asthma. Dried warm air (mean temp: +/- 1SD: 25.4 +/- 1.6 degrees C) and cold air (-19.7 +/- 2.6 degrees C) were breathed for 10 minutes each during quiet breathing at rest prior to as well as during both measurements of forced expired spirograms and the phase 3 slope of the single-breath oxygen test (delta N2/L). Subjects were also challenged with inhaled aerosolized histamine to determine the concentration required to reduce the forced expired volume in one second (FEV1) by 20 percent (PC20). Both asthmatic and control subjects had significantly greater respiratory heat exchange breathing cold as compared to warm air (p less than 0.01 in both cases). Control subjects did not change FEV1 or delta N2/L breathing cold air. Asthmatic patients increased delta N2/L from a mean warm air value of 2.41 +/- 1.31% N2/L to a mean cold air value of 5.39 +/- 4.55% N2/L (p less than 0.05). There was a significant linear correlation between the percent increase in delta N2/L from warm to cold air and 1/log10PC20 (r = -0.97, p less than 0.001) and also the percent decrease in FEV1 and log PC20 (r = -0.76, p less than 0.03) in the asthmatic patients. We conclude that cold air-induced alterations in ventilation/distribution and expired flow rates in asthmatic patients are related to pre-existing nonspecific airways reactivity.

Methacholine challenge: test-shortening procedures.

STUDY OBJECTIVES: Validation of test-shortening procedures for the 2-min tidal breathing methacholine challenge method. DESIGN: Retrospective chart review. SETTING: Tertiary-care university clinical pulmonary function laboratory. PATIENTS: One thousand subjects aged 10 to 85 years (mean +/- SD, 44.5 +/- 16.0 years), 44.5% male, referred for methacholine challenge. INTERVENTION: Two-minute tidal breathing methacholine challenge was performed, with both physician and technician access to published test-shortening procedures. MEASUREMENTS AND RESULTS: There were 315 positive test results (provocative concentration of methacholine causing a 20% fall in FEV(1) [PC(20)] < or = 8 mg/mL) and 685 negative test results. The subjects with positive test results were less likely to be male (39.1 vs 47.5%; p < 0.02) and had lower FEV(1) (91.8 +/- 14.9% predicted vs 97.2 +/- 13.9% predicted; p < 0.001). The average starting PC(20) was between 0.5 mg/mL and 1.0 mg/mL; the most common PC(20) was 1 mg/mL (67%). There were 431 skipped concentrations in 380 subjects. The mean number of methacholine inhalations was 3.7 +/- 1.1 (3.9 +/- 0.1 for negative test results vs 3.3 +/- 1.2 for positive test results; p < 0.001). Eighteen subjects had a > or = 20% FEV(1) fall on the first inhalation, and 11 subjects had a > or = 20% FEV(1) fall after a skipped concentration. In only one case (0.1%) an FEV(1) fall > or = 40% on the first concentration was reported, compared with no cases after a skipped concentration and seven cases with a > or = 40% FEV(1) fall after a routine doubling dose step-up. CONCLUSIONS: The 2-min tidal breathing methacholine test in clinical practice can be safely shortened to an average of less than four inhalations using starting concentrations based on FEV(1), asthma medication, and clinical features, and by occasionally omitting concentrations.

Sensitivity and specificity of early diagnostic tests of lung function in smokers.

What are the relative sensitivities and specificities of the "early" tests of lung dysfunction? We describe the findings from a study of virtually the entire population of a rural pollution-free community. Using abnormal spirometry as a marker of obstructive disease, we evaluated the two tests obtained from the single-breath nitrogen curve, closing volume (CV/VC) and the slope of the alveolar plateau (delta N2/L), as well as combinations of the two tests. While CV/VC is highly specific (92.3 percent in male and 94.0 percent in female subjects), it lacks sensitivity (36.8 percent in male and 13.3 percent in female subjects) and is abnormal in only 10.0 and 6.5 percent of male and female smokers, respectively, a percentage not dissimilar from the percentage with abnormal spirometry. However, delta N2/L, abnormal in 24.1 percent of male smokers and 28.8 percent of female smokers, rates reasonably well with regard to both sensitivity (63.2 percent in male and 66.7 percent in female subjects) and specificity (79.3 percent in male and 74.0 percent in female subjects). The group of smokers with abnormal delta N2/L did include fair numbers with abnormal spirometry (20.7 percent in male and 16.1 percent in female subjects). A combination of the two tests (abnormal in either delta N2/L and/or CV/VC) has good sensitivity (68.4 and 80.0 percent for male and female subjects, respectively) and specificity (74.3 and 69.0 percent for male and female subjects, respectively).

Routine pulse oximetry during methacholine challenges is unnecessary for safety.

BACKGROUND: Methacholine-induced bronchoconstriction is associated with significant hypoxemia, which can be assessed noninvasively by transcutaneous oxygen tension and pulse oximetry. OBJECTIVES: To assess the value of the monitoring of finger pulse oximetry during routine methacholine challenges in a clinical pulmonary function laboratory with regard to both safety and the possibility that a significant fall in oxygen saturation as measured by pulse oximetry (SpO(2)) might be a useful surrogate for determining the response to methacholine. METHODS: Two hundred consecutive patients undergoing diagnostic methacholine challenges in the pulmonary function laboratory of a tertiary-care, university-based referral hospital were studied. Methacholine challenges were performed by the standardized 2-min tidal breathing technique, and the DeltaFEV(1) was calculated from the lowest postsaline solution inhalation to the lowest postmethacholine inhalation value. SpO(2) was measured immediately prior to each spirogram, and the DeltaSpO(2) was measured from the lowest postsaline solution inhalation value to the lowest postmethacholine inhalation value. We examined the data for safety (ie, any SpO(2) value < 90). Based on previous reports, we used a DeltaSpO(2) of > or = 3 as significant and looked at the sensitivity, specificity, and positive and negative predictive values for DeltaSpO(2) > or = 3 vis-à-vis a fall in FEV(1) of > or = 15%. RESULTS: There were 119 nonresponders (DeltaFEV(1), < 15%) and 81 responders. The baseline FEV(1) percent predicted was slightly but significantly lower in the responders (responders [+/- SD], 91.6 +/- 15%; nonresponders, 96.4 +/- 14%; p < 0.05). DeltaSpO(2) was 3.1 +/- 1.6 in the responders and 1.6 +/- 1.8 in the nonresponders (p < 0. 001). There was a single recording in one patient of SpO(2) < 90 (88). A DeltaSpO(2) > or = 3 had a sensitivity of 68%, a specificity of 73%, a positive predictive value of 63%, and negative predictive value of 77% for a fall in FEV(1) > or = 15%. CONCLUSIONS: Pulse oximetry is not routinely useful for safety monitoring during methacholine challenge. DeltaSpO(2) is not helpful in predicting a positive spirometric response to methacholine. However, the negative predictive value is adequate to allow the DeltaSpO(2) to be used as an adjunct in assessing a negative result of a methacholine test in patients who have difficulty performing spirometry.

Effect of volume history on changes in DLcoSB-3EQ with lung volume in normal subjects.

The purpose of this study was to determine the relationship between the three-equation diffusing capacity for carbon monoxide (DLcoSB-3EQ) and lung volume and to determine how this relationship was altered when maneuvers were immediately preceded by a deep breath. DLcoSB-3EQ maneuvers were performed in nine healthy subjects either immediately after a deep breath or after tidal breathing for 10 min. The maneuvers consisted of slow inhalation of test gas from functional residual capacity to 25, 50, 75, or 100% of the inspiratory capacity and, without breath holding, slow exhalation to residual volume. After either a deep breath or tidal breathing, we found that DLcoSB-3EQ decreased nonlinearly with decreasing lung volume. At all lung volumes, DLcoSB-3EQ was significantly greater when measured after a deep breath than after tidal breathing. This effect increased as lung volume decreased, so that the greatest difference between DLcoSB-3EQ after a deep breath and that after tidal breathing occurred at the lowest lung volume. We conclude that a deep breath or spontaneous sigh has a role in reestablishing the pathway for gas exchange during tidal breathing.

Effect of breath-hold time on DLCO(SB) in patients with airway obstruction.

The single-breath diffusing capacity of the lung for CO [DLCO(SB)] is considered a measure of the conductance of CO across the alveolar-capillary membrane and its binding with hemoglobin. Although incomplete mixing of inspired gas with alveolar gas could theoretically influence overall diffusion, conventional calculations of DLCO(SB) spuriously overestimate DLCO(SB) during short breath-holding periods when incomplete mixing of gas within the lung might have the greatest effect. Using the three-equation method to calculate DLCO(SB) which analytically accounts for changes in breath-hold time, we found that DLCO(SB) did not change with breath-hold time in control subjects but increased with increasing breath-hold time in both patients with asthma and patients with emphysema. The increase in DLCO(SB) with increasing breath-hold time correlated with the phase III slope of the single-breath N2 washout curve. We suggest that in patients with ventilation maldistribution, DLCO(SB) may be decreased for the shorter breath-hold maneuvers because overall diffusion is limited by the reduced transport of CO from the inspired gas through the alveolar gas prior to alveolar-capillary gas exchange.

Effect of lung volume on ventilation distribution.

To examine the effect of preinspiratory lung volume (PILV) on ventilation distribution, we performed multiple-breath N2 washouts (MBNW) in seven normal subjects breathing 1-liter tidal volumes over a wide range of PILV above closing capacity. We measured the following two independent indexes of ventilation distribution from the MBNW: 1) the normalized phase III slope of the final breaths of the washout (Snf) and 2) the alveolar mixing efficiency during that portion of the washout where 80-90% of the lung N2 had been cleared. Three of the subjects also performed single-breath N2 washouts (SBNW) by inspiring 1-liter breaths and expiring to residual volume at PILV = functional residual capacity (FRC), FRC + 1.0, and FRC - 0.5, respectively. From the SBNW we measured the phase III slope over the expired volume ranges of 0.75-1.0, 1.0-1.6, and 1.6-2.2 liters (S0.75, S1.0, and S1.6, respectively). Between a PILV of 0.92 +/- 0.09 (SE) liter above FRC and a PILV of 1.17 +/- 0.43 liter below FRC, Snf decreased by 61% (P less than 0.001) and alveolar mixing efficiency increased from 80 to 85% (P = 0.05). In addition, Snf and alveolar mixing efficiency were negatively correlated (r = 0.74). In contrast, over a similar volume range, S1.0 and S1.6 were greater at lower PILV. We conclude that, during tidal breathing in normal subjects, ventilation distribution becomes progressively more inhomogeneous at higher lung volumes over a range of volumes above closing capacity.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of airway closure on ventilation distribution.

We examined the effect of airway closure on ventilation distribution during tidal breathing in six normal subjects. Each subject performed multiple-breath N2 washouts (MBNW) at tidal volumes of 1 liter over a range of preinspiratory lung volumes (PILV) from functional residual capacity (FRC) to just above residual volume. All subjects performed washouts at PILV below their measured closing capacity. In addition five of the subjects performed MBNW at PILV below closing capacity with end-inspiratory breath holds of 2 or 5 s. We measured the following two independent indexes of ventilation maldistribution: 1) the normalized phase III slope of the final breaths of the washout (Snf) and 2) the alveolar mixing efficiency of those breaths of the washout where 80-90% of the initial N2 had been cleared. Between a mean PILV of 0.28 liter above closing capacity and that 0.31 liter below closing capacity, mean Snf increased by 132% (P less than 0.005). Over the same volume range, mean alveolar mixing efficiency decreased by 3.3% (P less than 0.05). Breath holding at PILV below closing capacity resulted in marked and consistent decreases in Snf and increases in alveolar mixing efficiency. Whereas inhomogeneity of ventilation decreases with lung volume when all airways are patent (J. Appl. Physiol. 66: 2502-2510, 1989), airway closure increases ventilation inequality, and this is substantially reduced by short end-inspiratory breath holds. These findings suggest that the predominant determinant of ventilation distribution below closing capacity is the inhomogeneous closure of airways subtending regions in the lung periphery that are close together.

Effect of ventilation inhomogeneity on "intrabreath" measurements of diffusing capacity in normal subjects.

In normal seated subjects we increased single-breath ventilation inhomogeneity by changing both the preinspiratory lung volume and breath-hold time and examined the ensuing effects on two different techniques of measuring the diffusing capacity of the lung for carbon monoxide (DLCO). We measured the mean single-breath DLCO using the three-equation method (DLCOSB-3EQ) and also measured DLCO over discrete intervals during exhalation by the "intrabreath" method (DLCOexhaled). We assessed the distribution of ventilation using the normalized phase III slope for helium (SN). DLCOSB-3EQ was unaffected by preinspiratory lung volume and breath-hold time. DLCOexhaled increased with increasing preinspiratory lung volume and decreased with increasing breath-hold time. These changes correlated with the simultaneously observed changes in ventilation inhomogeneity as measured by SN (P < 0.01). We conclude that measurements of DLCOexhaled do not accurately reflect the mean DLCO. Intrabreath methods of measuring DLCO are based on the slope of the exhaled CO concentration curve, which is affected by both ventilation and diffusion inhomogeneities. Although DLCOexhaled may theoretically provide information about the distribution of CO uptake, the concomitant effects of ventilation nonuniformity on DLCOexhaled may mimic or mask the effects of diffusion nonuniformity.

Measurement of temporal changes in DLSBCO-3EQ from small alveolar samples in normal subjects.

The dynamic changes in CO concentration [CO] during a single breath could be influenced by topographic inhomogeneity in the lung or by peripheral inhomogeneity due to a gas mixing resistance in the gas phase of the lung or to serial gradients in gas diffusion. Ten healthy subjects performed single-breath maneuvers by slowly inhaling test gas from functional residual capacity to one-half inspiratory capacity and slowly exhaling to residual volume with target breath-hold times of 0, 1.5, 3, 6, and 9 s. We calculated the three-equation single-breath diffusing capacity of the lung for CO (DLSBCO-3EQ) from the mean [CO] in both the entire alveolar gas sample and in four successive equal alveolar gas samples. DLSBCO-3EQ from the entire alveolar gas sample was independent of breath-hold time. However, with 0 s of breath holding, from early alveolar gas samples DLSBCO-3EQ was reduced and from late alveolar gas samples it was increased. With increasing breath-hold time, DLSBCO-3EQ from the earliest alveolar gas sample rapidly increased, whereas from the last alveolar gas sample it rapidly decreased such that all values from the small alveolar gas samples approached DLSBCO-3EQ from the entire alveolar sample. These changes correlated with ventilation inhomogeneity, as measured by the phase III He concentration slope and the mixing efficiency, and were larger for maneuvers with inspired volumes to one-half inspiratory capacity vs. total lung capacity.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of ventilation inhomogeneity on DLcoSB-3EQ in normal subjects.

In patients with airflow obstruction, we found that ventilation inhomogeneity during vital capacity single-breath maneuvers was associated with decreases in the three-equation single-breath CO diffusing capacity of the lung (DLcoSB-3EQ) when breath-hold time (tBH) decreased. We postulated that this was due to a significant resistance to diffusive gas mixing within the gas phase of the lung. In this study, we hypothesized that this phenomenon might also occur in normal subjects if the breathing cycle were altered from traditional vital capacity maneuvers to those that increase ventilation inhomogeneity. In 10 normal subjects, we examined the tBH dependence of both DLcoSB-3EQ and the distribution of ventilation, measured by the mixing efficiency and the normalized phase III slope for helium. Preinspiratory lung volume (V0) was increased by keeping the maximum end-inspiratory lung volume (Vmax) constant or by increasing V0 and Vmax. When V0 increased while Vmax was kept constant, we found that the tBH-independent and the tBH-dependent components of ventilation inhomogeneity increased, but DLcoSB-3EQ was independent of V0 and tBH. Increasing V0 and Vmax did not change ventilation inhomogeneity at a tBH of 0 s, but the tBH-dependent component decreased. DLcoSB-3EQ, although independent of tBH, increased slightly with increases in Vmax. We conclude that in normal subjects increases in ventilation inhomogeneity with increases in V0 do not result in DLcoSB-3EQ becoming tBH dependent.

Facial erysipelas in the immunocompromised host. Report of two cases.

Two cases of facial erysipelas in immunologically altered hosts are reported herein. The unusual presentation with absence of erythema in the skin lesion is emphasized. Atypical fever patterns were also noted. In one patient, the facial lesion followed the onset of fever by 48 hours, and, in the other, the facial swelling preceded the fever. Various aspects of the patient's altered host status are discussed in light of the atypical clinical presentation. Recognition of facial erysipelas as a potential source of group A beta-hemolytic streptococcemia in immune-altered hosts is important to ensure rapid and appropriate therapeutic intervention.

Diffusing capacity in the clinical assessment of chronic airflow limitation.

CAL remains an important cause of morbidity and mortality. The diffusing capacity has ranked high in the assessment of CAL because it represents the best pulmonary function test to assess the integrity of the pulmonary capillary bed. Unfortunately, numerous physiologic, pathologic, and technical factors affect the test, thus limiting its sensitivity and specificity. HRCT techniques offer the potential to assess the extent of emphysema more accurately, but the technique requires greater standardization and is more expensive and less noninvasive than DLcoSB testing. Although the CIBA symposium considered DLcoSB "essential" in the investigation of the CAL patient, 16 the use of conventional DLcoSB testing in the seated position at rest is not currently advised as a routine screening procedure. The test must be performed in a center with high degree of quality control, and the results can be of value only by integrating the result into a comprehensive clinical assessment. Within this context, conventional DLcoSB testing may provide limited information about the extent of emphysema because reductions in DLcoSB correlate with the extent of emphysema by HRCT. When DLcoSB is normal, it may point in the direction of considering asthma as the cause of the airflow limitation. It may also provide information about disease severity and prognosis in O2-dependent CAL patients. The test should be a part of the investigation of the patient with unexplained dyspnea. It remains controversial how emphysema correlates with the degree of impairment in CAL, and further work needs to be done to clarify this relationship. This requires a reexamination of current CT methods 110 and the relationship between DLcoSB, structural changes in the lung, and HRCT evidence of emphysema. Refinements in DLcoSB testing methods, such as the measurement of DLcoSB-3EQ are linked to rapidly responding CO analyzers and computer-driven software, which will potentially improve the accuracy and reproducibility of the test, particularly in the presence of airway obstruction and nonuniform distribution of ventilation. Such refinements, which offer the possibility that tests of diffusion could become more useful markers of disease, include measuring DLcoSB when the pulmonary capillary recruitment is near maximal (head-down position, exercise), enhancing the sensitivity of the test to alterations in the lung periphery, standardizing previous volume history, developing more precise corrections for Hb and COHb, and developing an index of diffusion nonuniformity.