Poor adherence to HIV monitoring and treatment guidelines for HIV-infected injection drug users.

OBJECTIVES: There is growing concern about access to HIV/AIDS care among injection drug users (IDUs). We examined rates of CD4 cell count monitoring and correlates among HIV-infected IDUs. METHODS: This prospective observational cohort study of 460 community-recruited HIV-infected IDUs was situated in a Canadian city where all medical care is provided free of charge. Over a median follow-up period of 76 months, we evaluated factors associated with CD4 cell count monitoring through a linkage with a centralized CD4 registry. RESULTS: Overall, <5% of IDUs had CD4 monitoring consistent with local therapeutic guidelines. In multivariate analyses, after adjustment for being on antiretroviral therapy [odds ratio (OR) 2.21, 95% confidence interval (CI) 1.84-2.70, P<0.001] female gender (OR 0.71, 95% CI 0.57-0.89, P=0.003), non-White ethnicity (OR 0.75, 95% CI 0.60-0.94, P=0.014), use of methadone maintenance therapy (OR 1.66, 95% CI 1.42-1.94, P<0.001) and daily heroin use (OR 0.72, 95% CI 0.61-0.85, P<0.001) were independently associated with CD4 monitoring. CONCLUSIONS: Strategies to improve CD4 surveillance among IDUs are critically important, particularly for female and non-White IDUs. Expanded treatment for heroin dependence appears to have the greatest potential for improved care.

Unexpected lung lesions in high resolution computed tomography (HRTC) among patients with advanced HIV disease.

The present pilot study was undertaken to characterize the frequency of lung lesions in asymptomatic human deficiency virus (HIV) infected individuals with advanced HIV disease. Thirty two consecutive HIV+ homosexual males assessed for initiation of Pneumocystis carinii pneumonia (PCP) prophylaxis, were prospectively studied. All patients underwent a complete medical history, physical examination, pulmonary function tests and high resolution computed tomography (HRCT). HRCT scans were read by a single radiologist, who was blind as to the clinical status of the patient. Unexpected HRCT scan lesions were found in 60% of patients. There were no statistically significant differences between patients with normal and abnormal HRCT with respect to age, height, weight, CD4+ count, smoking history, serum albumin, alpha 1-antitrypsin level or body mass index. Forced vital capacity (FVC) (% of predicted) and peak expiratory flow rate (PEFR) (% pred) were not significantly different between groups. For patients with normal and abnormal HRCT forced expiratory volume in one second (FEV1) (% pred) was 99 +/- 12 vs 92 +/- 16, FEV1/FVC was 82 +/- 5 vs 76 +/- 9, and forced mid-expiratory flow (FEF25-75) (% pred) was 100 +/- 24 vs 77 +/- 27, respectively. There were no statistically significant differences between patients presenting with destructive versus nondestructive lung HRCT lesions. Our results demonstrate that as many as 60% of HIV-infected patients have unexpected abnormalities on HRCT at the time of starting PCP prophylaxis. We speculate that these lesions may contribute to the high frequency of spontaneous pneumothoraces previously reported in this patient population.

Density dependence of pulmonary resistance: correlation with small airway pathology.

The density dependence of maximal expiratory flow is not an effective test of the site of airway narrowing in obstructive lung disease. We hypothesized that the density dependence of pulmonary resistance (DD,RL) would be more closely related to the degree of airway narrowing and peripheral airway pathology in smokers. We measured maximal expiratory flow at 50% vital capacity (V'max50) and lung resistance (RL) breathing air and 80% helium-20% oxygen, and calculated density dependence of V'max50 and RL in 40 patients who had moderate airflow obstruction and in 10 normal subjects. We compared the density dependence of RL and V'max50 with the degree of airway obstruction and bronchiolar pathology scores in 27 patients with resected lung specimens. There were no differences in DD of V'max50 or RL between normal subjects and patients, and no relationship between the degree of obstruction or the bronchiolar pathology score and the DD of these measurements. There were significant relationships between V'max50, RL and the bronchiolar pathology scores. In conclusion, lung resistance and maximal expiratory flow are related to the severity of peripheral airway pathology, but there is no relationship between the severity of obstruction or the severity of peripheral airway pathology and the density dependence of maximal expiratory flow or lung resistance.

Decreasing frequency but worsening mortality of acute respiratory failure secondary to AIDS-related Pneumocystis carinii pneumonia.

OBJECTIVE: To describe changes in incidence and outcome of acute respiratory failure (ARF) due to AIDS-related Pneumocystis carinii pneumonia (PCP) at a tertiary care center over the 4-year period starting April 1, 1987 with reference to previously reported data from the preceding 6 years. METHODS: All patients admitted to St. Paul's hospital with a diagnosis of AIDS-related PCP during the study period were reviewed with regard to diagnostic, clinical, therapeutic, and outcome variables. RESULTS: A total of 456 episodes of PCP were diagnosed during the study period. These were compared against 127 cases diagnosed between 1981 and 1987. The frequency of hospitalization for PCP decreased to 78% in 1987 to 1991 from 100% in 1981 to 1987 (p < or = 0.001). A similar decreasing trend was observed with regard to the incidence of PCP-related ARF that declined from 21% in 1981 to 1987 to 9% in 1987 to 1991 (p = 0.009). Despite this, overall PCP-related mortality remained stable at 12% in 1981 to 1987 and 9% in 1987 to 1991 (p = 0.26). The proportion of patients with PCP-related ARF who received mechanical ventilation decreased from 89% in 1981 to 1987 to 64% in 1987 to 1991 (p < 0.001). Despite this, the case fatality rate among mechanically ventilated patients increased from 50% in 1981 to 1987 to 89% in 1987 to 1991 (p = 0.003). These changes were associated with a significant change in the pattern of use of corticosteroids as adjunctive therapy for AIDS-related PCP. In 1985 to 1986, nearly 100% of patients admitted to the ICU received corticosteroids only after admission to the ICU, following the development of ARF. In contrast, in 1989 to 1990, 50% of patients were admitted to the ICU already receiving systemic corticosteroids. The rise in the proportion of patients receiving corticosteroids prior to ICU admission between these two intervals was statistically significant (p = 0.017). CONCLUSION: Our data show a decreasing frequency but a worsening mortality of ARF secondary to AIDS-related PCP. We conclude that ARF secondary to AIDS-related PCP developing despite maximal therapy, including adjunctive corticosteroids, carries a dismal prognosis.

Oral corticosteroids in patients with mild Pneumocystis carinii pneumonia and the acquired immune deficiency syndrome (AIDS).

OBJECTIVE: To assess the effect of oral corticosteroids in patients with mild Pneumocystis carinii pneumonia and the acquired immune deficiency syndrome (AIDS). DESIGN: Prospective, double blind, placebo controlled, randomized trial. METHODS: Included were AIDS patients having their first episode of P. carinii pneumonia, who had no other known active pulmonary pathology, who had no contraindications for corticosteroids and who had received no other anti-P. carinii medications for more than 48 h. Subjects received either prednisone, 60 mg/day for 7 days, followed by a progressive tapering over 14 days, or identical placebo. The present analysis pertains to patients with mild P. carinii pneumonia as defined by a baseline resting oxygen saturation greater than 90% and a decrease in oxygen saturation during exercise while breathing room air of not less than 5 percentage points. Early deterioration, the end-point of the trial, was defined as a 10% decrease from baseline oxygen saturation on day 3 or thereafter. RESULTS: At study termination, there were 12 subjects in the placebo group and 11 in the corticosteroid group. Baseline characteristics were not statistically different between the treatment groups. Early deterioration developed in 7 and 1 patients in the placebo and corticosteroid groups respectively (P = 0.027). In addition, by day 3, a number of parameters were less favorable in the placebo group relative to the corticosteroid group including median oxygen saturation (85% vs 97%; P = 0.003), lactic dehydrogenase (1514 vs 763; P = 0.013), median respiratory rate (30 vs 22; P = 0.003), median heart rate (100 vs 81; P = 0.002), and median temperature (39 vs 37; P = 0.024). Even though patients suffering early deterioration in the placebo group were switched to corticosteroids, significant differences between the groups remained at day 30 with regard to exercise tolerance. More than half of patients assigned to the corticosteroid group exercised for a median of 6.5 min on day 30 (P = 0.017). CONCLUSION: Oral corticosteroids prevent early deterioration and increase exercise tolerance in patients with mild AIDS-related P. carinii pneumonia as defined on the basis of pulse oximetry.

Effect of breathing pattern during inhalation challenge on the shape and position of the dose-response curve.

To examine the effect of breathing pattern on the dose-response curve, 4 mild asthmatic and 9 normal subjects inhaled increasing concentrations of methacholine (0.03-256 mg/ml) using a quiet tidal breathing pattern or tidal breathing with a forced expiratory phase. The provocative concentration of methacholine causing a 20% decrease in the forced expired volume in 1 s (PC20FEV1) or a 200% increase in pulmonary resistance (PC 200RL) was determined. In addition, the maximal change in FEV1 and RL and the slopes of the dose-response curves were measured. The forced expiratory pattern caused an increase in the central/peripheral deposition ratio of a [99m]technetium-labeled aerosol (n = 3). There were no differences in mean tidal volume, minute ventilation, inspiratory flow rates, or baseline FEV1 or RL between the quiet breathing or forced expiration studies, although mean expiratory flows were increased in the latter (p less than 0.001). PC20FEV1 and PC200 RL decreased (p less than 0.001) but the maximal change in FEV1 and RL was unchanged in the forced expiration studies. Forced expiration during inhalation challenge did not alter the slope of FEV1 or RL dose-response curves. These results suggest that the sensitivity (PC20, PC200) and maximal response of in vivo dose-response curves may be affected independently by factors such as aerosol deposition.

Tracheobronchial and upper airway blood flow in dogs during thermally induced panting.

Tracheobronchial blood flow increases two- to fivefold in response to isocapnic hyperventilation with warm dry or cold dry air in anesthetized, tracheostomized dogs. To determine whether this response is governed by central nervous system thermoregulatory control or is a local response to the drying and/or cooling of the airway mucosa, we studied eight anesthetized spontaneously breathing dogs in a thermally controlled chamber designed so that inspired air temperature, humidity, and body temperature could be separately regulated. Four dogs breathed through the nose and mouth (group 1), and four breathed through a short tracheostomy tube (group 2). Dogs were studied under the following conditions: 1) a normothermic control period and 2) two periods of hyperthermia in which the dogs panted with either warm 100% humidified air or warm dry (approximately 10% humidified) air. Radiolabeled microspheres (15 +/- 3 micron diam) were injected into the left ventricle as a marker of nasal, lingual, and tracheobronchial blood flow. After the final measurements, the dogs were killed and tissues of interest excised. Results showed that lingual and nasal blood flow (ml.min-1.g-1) increased during panting (P less than 0.01) in both groups and were not affected by the inspired air conditions. In group 1, tracheal mucosal blood flow barely doubled (P less than 0.01) and bronchial blood flow did not change during humid and dry air panting. In group 2, there was a sevenfold increase in tracheal mucosal and about a threefold increase in bronchial blood flow (P less than 0.01), which was only observed during dry air panting.(ABSTRACT TRUNCATED AT 250 WORDS)

Site of bronchodilatation with inhaled ipratropium bromide and fenoterol in normal subjects.

To assess the effectiveness and site of action of bronchodilatation with an inhaled anticholinergic bronchodilator, ipratropium bromide, and a beta adrenergic agonist, fenoterol, we measured the density dependence of maximal flow and the density dependence of pulmonary resistance using a digital computerized averaging circuit. Eight normal subjects were studied on two separate days, before and after the bronchodilators were administered in a double blind manner. Both drugs resulted in significant and equivalent bronchodilatation. However, there were no significant changes in the density dependence of maximal flow or pulmonary resistance with either agent. These results in normal subjects, therefore, do not support the hypothesis of a preferential site of action of inhaled anticholinergic agents and beta-adrenergic agents.

Inspiratory muscle function in unilateral diaphragmatic paralysis.

Pulmonary function has been extensively studied in unilateral diaphragmatic paralysis (UDP), but there is scarce information regarding inspiratory muscle function in this condition. We therefore studied inspiratory muscle function in 8 patients with UDP (Group 1: age 48.3 +/- 2.1 yr of age, means +/- SD) as well as in 7 patients with UDP and concomitant cardiopulmonary disease (Group 2: 60.6 +/- 13 yr of age). Twelve young normal subjects were also studied (32.3 +/- 7.7 yr of age). Maximal static transdiaphragmatic and inspiratory mouth pressure were measured at FRC. Gastric (Pga), esophageal (Pes), and transdiaphragmatic (Pdi) pressure swings were measured during quiet breathing. There was no difference in inspiratory muscle function in left-sided versus right-sided UDP. Paradoxical gastric pressure swings were observed in 4 patients from Group 1 and in 5 from Group 2. In 2 patients from Group 1 and 1 from Group 2, Pga did not change during quiet breathing. In the remaining 3 patients, Pga swings were similar to those observed in the normal subjects. Maximal Pdi was reduced in half of the patients from Group 1 and in all of the patients from Group 2. Maximal inspiratory pressure was below normal values in 2 patients from Group 1 and in all patients from Group 2. We conclude that unilateral diaphragmatic paralysis is associated with an abnormal pattern of use of respiratory muscles during quiet breathing, characterized by the use of intercostal and accessory inspiratory muscle or compensatory use of abdominal expiratory muscles. Inspiratory muscle strength was impaired in some of the patients, and it worsened when cardiopulmonary disease was present.