Horst Baier

Corticosteroids as adjunctive therapy for severe Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome: a double-blind, placebo-controlled trial.

BACKGROUND Preliminary reports suggest that patients with the acquired immunodeficiency syndrome (AIDS) and Pneumocystis carinii pneumonia may benefit from the addition of corticosteroid treatment to antibiotic therapy. METHODS We conducted a double-blind, placebo-controlled trial to assess the efficacy of adjunctive corticosteroids in patients with AIDS and severe P. carinii pneumonia. Patients with marked abnormalities in gas exchange who had been treated with antibiotics for less than 72 hours were randomly assigned to receive either methylprednisolone (40 mg) or placebo every 6 hours for 7 days, in addition to treatment for 21 days with trimethoprim-sulfamethoxazole. The primary outcome measures were survival until hospital discharge and the development of respiratory failure. RESULTS Twenty-three patients were enrolled in the study; there were no significant differences in base-line clinical or laboratory measures between the two treatment groups. Of 12 patients treated with corticosteroids, 9 (75 percent) survived until hospital discharge, as compared with only 2 of 11 placebo recipients (18 percent) (P less than 0.008). Respiratory failure developed in nine placebo recipients, as compared with only three patients treated with corticosteroids (P less than 0.008). No patient required the interruption or discontinuation of corticosteroid or antibiotic treatment because of toxicity or a complicating event. Because of the marked difference in survival, it was deemed unethical to continue the trial, and the study was terminated. CONCLUSIONS Early adjunctive corticosteroid therapy can improve survival and decrease the occurrence of respiratory failure in patients with AIDS and severe P. carinii pneumonia.

Incidence of pulmonary barotrauma in a medical ICU.

One hundred seventy-one patients admitted to a Medical ICU and who received treatment for respiratory failure with mechanical ventilation were studied for the development of pulmonary barotrauma (PBT) as manifested by pneumomediastinum, subcutaneous emphysema, or pneumothorax. Fourteen patients (8%; group A) developed this complication; they were younger, had higher maximal peak inspiratory airway pressures (PIP); and higher levels of maximal PEEP.We conclude that for medical patients treated for respiratory failure with mechanical ventilation, the incidence of PBT is 8% and that younger age, higher levels of PIP and PEEP seem to pose an increased risk for developing PBT.

Evidence for increased permeability in reexpansion pulmonary edema

Concurrent analyses of the colloid osmotic pressure of pulmonary edema fluid and serum were performed in two patients with reexpansion pulmonary edema. In addition, pulmonary artery wedge pressure was measured during pulmonary edema in one patient. The colloid osmotic pressure of the pulmonary edema fluid was 73 and 81 percent of the serum value. The pulmonary arterial wedge pressure in one patient was within normal limits (8 mm Hg). Reexpansion pulmonary edema appears to be due to increased pulmonary capillary permeability rather than to hemodynamic mechanisms.

Bronchial circulation in asthma

Whereas the anatomical changes of the bronchial circulation in response to a wide variety of congenital and acquired cardiopulmonary diseases have been well described, little is known about its functional response. There is growing evidence that the bronchial circulation plays a major role in the pathophysiology of hyperreactive airway disease. The bronchial vascular system appears to be involved in mediator transport to and from target tissues in the airway wall, in the development of airway wall edema which may contribute to airflow obstruction, and in heat and water exchange in the tracheobronchial tree. Although our current understanding of these functions is rather sketchy, enough is known to outline the contributions of the bronchial, i.e. the systemic circulation to the mechanisms of bronchial asthma.

Clinical Characteristics of Subjects With Symptoms of α1-Antitrypsin Deficiency Older Than 60 Years

BACKGROUND The clinical characteristics of elderly subjects with alpha(1)-antitrypsin deficiency (AATD)-associated COPD have not been described. METHODS The clinical, demographic, health-related quality of life (HRQoL) characteristics and 1-year exacerbation rates of 275 subjects with AATD and COPD receiving augmentation therapy aged > 59 years (mean [+/- SD] age, 66.3 +/- 5.7 years) were compared to those of 354 subjects aged 50 to 59 years (mean age, 54.3 +/- 2.8 years) and 293 subjects < 50 years (mean age, 43.9 +/- 3.8 years). RESULTS Older subjects received diagnoses later in life (mean age at diagnosis, 55.0 +/- 8.5 years) and had a longer diagnostic delay (mean age at diagnosis, 12.9 +/- 14.3 years) than subjects in the other two age groups. Although the proportion of lifetime nonsmokers was higher in the older group, the majority (64%) had significant tobacco exposure but with a longer interval of tobacco abstinence. The mean FEV(1) values (n = 641) were similar between the three age groups, suggesting a slower disease progression in the oldest group. Subjects in the older group were less symptomatic, had less concomitant asthma, and had significantly better scores in most domains of two HRQoL instruments. During follow-up, older subjects had fewer acute exacerbations. CONCLUSIONS Subjects with AATD-associated COPD who reach an older age exhibit a more indolent clinical course than younger affected individuals, possibly related in part to differences in tobacco exposure. This finding supports current guidelines that recommend screening of all patients with COPD for AATD, regardless of their age and prior smoking history.

Exacerbations in subjects with alpha-1 antitrypsin deficiency receiving augmentation therapy.

BACKGROUND The frequency, characteristics and impact of acute exacerbations in patients with alpha-1 antitrypsin deficiency (AATD) and COPD who are on intravenous alpha-1 antitrypsin augmentation therapy have not been described. METHODS 922 subjects with AATD and COPD on augmentation therapy (mean age 54.5 years) were followed with monthly telephone surveys to record exacerbation characteristics, as well as healthcare resource utilization and health-related quality of life (HRQoL). Exacerbations were defined by symptom-based and healthcare resource utilization (HRU) criteria. RESULTS During the 1-year follow-up, 91.5% of participants experienced at least one exacerbation (mean 2.4 exacerbations per subject, median 2, and mean duration 17 days per episode, regardless of the definition used). Most exacerbations were categorized as severe by symptoms and moderate by HRU criteria. Subjects who had 3 or more exacerbations (48.6%) were younger, had higher medication use and had higher tobacco consumption compared with subjects with less exacerbations. Subjects with frequent exacerbations had the worst baseline HRQoL scores, as well as more physician visits, emergency room visits, and hospitalizations. Although most subjects received augmentation therapy on a weekly basis, other infusion schedules were more commonly observed in subjects with fewer exacerbations. CONCLUSION COPD exacerbations occur frequently and are associated with significant disease burden in subjects with AATD receiving augmentation therapy.

Respiratory mechanics of the loggerhead sea turtle, Caretta caretta

Respiratory mechanics were evaluated in excised lungs and in spontaneously breathing loggerhead sea turtles (Caretta caretta). Respiratory compliance curves reflect the pressure volume characteristics of the body wall. Compliance values are comparable to those of reptiles having simpler lung structure. Maximum flow rates in excised lungs (18-25 ml.sec-1.kg-1) were only slightly below the range reported for marine mammals. During spontaneous tidal breathing expiratory flow rates (11.8 ml.sec-1.kg-1) were lower than maximum values. In the sea turtle, respiratory adaptations including reduced airway resistance and muscular contribution to breathing are similar to marine mammals. These mechanical specializations shorten breathing time, which contributes to diving performance.

Interactions of Isoniazid with Foods

We reviewed reactions previously reported in patients treated with isoniazid, who ate certain fish and cheeses. We observed similar reactions in two patients after they ingested cheese and wine. Isoniazid is an inhibitor of both monoamine and diamine oxidases, which contribute to the metabolism of histamine that may be present in some fish and cheeses. Monoamine oxidase also acts in the metabolism of tyramine, present in some cheeses and wines. Reactions reported after eating fish or cheese, in patients treated with isoniazid, are similar in that both are characterized by headache, palpitations, skin flushing, nausea, vomiting, and pruritus. Reactions after fish have not been associated with increased blood pressure, whereas those following cheese ingestion frequently result in modest increases in blood pressure. Patients treated with isoniazid should be alerted to the possibility of reactions after eating certain foods.

Quantitative gallium scanning in pulmonary sarcoidosis

Pulmonary parenchymal involvement in sarcoidosis is due to noncaseating granuloma, fibrosis or both. To assess the granulomatous activity in pulmonary sarcoidosis, we performed gallium-67 citrate scans in 41 patients with sarcoidosis and in 13 non-sarcoid patients, who were free of pulmonary disease and served as controls. Gallium score, a measure of gallium accumulation in lung parenchyma, was obtained from the sum of activity indices (ratio of accumulated gallium activity over a chest quadrant and soft tissues of the mid-thigh) from each of the quadrants over the anterior and posterior aspects of the chest. The gallium score in patients with sarcoidosis was significantly higher than the gallium score in controls. The gallium scores in patients with sarcoidosis, with radiographically apparent pulmonary infiltrate were significantly higher than the scores in the patients with no radiographic evidence of pulmonary parenchymal involvement. The gallium scores in patients not receiving corticosteroids were significantly higher compared to patients who were receiving corticosteroids, and furthermore, the gallium scores fell significantly when corticosteroids were initiated. There was a significant correlation between serum angiotensin-converting enzyme (SACE) activity and gallium score. In 11 patients, 27 sequential gallium scans were performed and changes in gallium score correlated well with the changes in SACE activity and clinical assessment. These findings suggest that quantitative evaluation of gallium scans may be useful in assessing granulomatous activity of pulmonary sarcoidosis and following its response to therapy.

Lung mechanical properties in the West Indian Manatee (Trichechus manatus)

Airway dimensions, extent of cartilage reinforcements and lung mechanical properties were examined in excised lungs of the West Indian Manatee (Trichechus manatus). All airways with a mean inside diameter of more than 0.6 mm had complete cartilaginous rings in their walls, and cartilage reinforcement extended into the respiratory bronchi. Expiratory flow rates over the vital capacity range were higher than those encountered in humans varying between 20 and 50% of peak flow at 25% of vital capacity. They were, however, lower than in other marine mammals. The ratio of lung compliance to lung weight was found to be 0.67 ml/(g X cm H2O) compared to 0.18 ml/(g X cm H2O) in terrestrial mammals. This together with a high gas-tissue ratio of 11 mg/g for the inflated manatee lung indicates that strong airway reinforcements are necessary to prevent airway collapse during exhalation.